Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-κB Are Required for Appropriate Inflammatory Responses and Immune Cell Homeostasis

Murphy, Evelyn; Crean, Daniel

doi:10.3390/biom5031302

Cited by 82Nuclear Receptors and SignalingNF-κB Signaling PathwaysSignaling Pathways in Disease

Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-κB Are Required for Appropriate Inflammatory Responses and Immune Cell Homeostasis

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Murphy, Evelyn, Crean, Daniel·2015·Biomolecules

DOI 10.3390/biom5031302PMC PMC4598753

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Abstract

Appropriate innate and adaptive immune responses are essential for protection and resolution against chemical, physical or biological insults. Immune cell polarization is fundamental in orchestrating distinct phases of inflammation, specifically acute phase responses followed by resolution and tissue repair. Dysregulation of immune cell and inflammatory responses is a hallmark of multiple diseases encompassing atherosclerosis, rheumatoid arthritis, psoriasis and metabolic syndromes. A master transcriptional mediator of diverse inflammatory signaling and immune cell function is NF-κB, and altered control of this key regulator can lead to an effective switch from acute to chronic inflammatory responses. Members of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors crosstalk with NF-κB to regulate immune cell function(s). Within the NR superfamily the NR4A1-3 orphan receptors have emerged as important regulators of immune cell polarization and NF-κB signaling. NR4A receptors modulate NF-κB activity in a dynamic fashion, either repressing or enhancing target gene expression leading to altered inflammatory outcome. Here we will discuss the pivotal role NR4A’s receptors play in orchestrating immune cell homeostasis through molecular crosstalk with NF-κB. Specifically, we will examine such NR4A/NF-κB interactions within the context of distinct cell phenotypes, including monocyte, macrophage, T cells, endothelial, and mesenchymal cells, which play a role in inflammation-associated disease. Finally, we review the therapeutic potential of altering NR4A/NF-κB interactions to limit hyper-inflammatory responses in vivo.

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Transcriptome revealed decreased expression of NR4A nuclear receptors (NR4A1, NR4A2, NR4A3) in hEDS/HSD cells.
“As further evidence of unbalanced inflammatory responses in patients’ cells, transcriptome revealed a decreased expression of the NR4A nuclear receptors (NR4A1, NR4A2, NR4A3), which act as transcriptional regulators of inflammatory responses mediated by NF-kB signaling [159,160,161].”
From Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes (2019) · cites this paper as [160]

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Background
Activation of Liver X Receptor Sensitizes Human Dendritic Cells to Inflammatory Stimuli
Törőcsik, D., Baráth, M., Benkő, S., Széles, L., Dezsö, B., Póliska, S., Hegyi, Z., Homolya, L., Szatmári, I., Lányi, Á., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902399 · Cited by 77 · see citing works
Deficiency of the NR4A Neuron-Derived Orphan Receptor-1 Attenuates Neointima Formation After Vascular Injury
Nomiyama, T., Zhao, Y., Gizard, F., Findeisen, H. M., Heywood, E. B., Jones, K. L., Conneely, O. M., & Bruemmer, D. (2009) · Circulation · doi:10.1161/circulationaha.108.822056 · Cited by 77 · see citing works
The Nurr1 Activator 1,1-Bis(3′-Indolyl)-1-(p-Chlorophenyl)Methane Blocks Inflammatory Gene Expression in BV-2 Microglial Cells by Inhibiting Nuclear Factor κB
Miranda, B. R. D., Popichak, K. A., Hammond, S. L., Jorgensen, B. A., Phillips, A. T., Safe, S. H., & Tjalkens, R. B. (2015) · Molecular Pharmacology · doi:10.1124/mol.114.095398 · Cited by 76 · see citing works
Liver X receptor agonists inhibit tissue factor expression in macrophages
Terasaka, N., Hiroshima, A., Ariga, A., Honzumi, S., Koieyama, T., Inaba, T., & Fujiwara, T. (2005) · FEBS Journal · doi:10.1111/j.1742-4658.2005.04599.x · Cited by 71 · see citing works
Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-1/TR3 and nuclear factor- B
Harant, H. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh856 · Cited by 69 · cited 1× · see citing works
“expression of IL-2 via negative regulation of NF- B activity [59].”
Background
Peroxisome Proliferator-Activated Receptor γ Ligands Improve the Antitumor Efficacy of Thrombospondin Peptide ABT510
Huang, H., Campbell, S. C., Bedford, D. F., Nelius, T., Veliceasa, D., Shroff, E. H., Henkin, J., Schneider, A. J., Bouck, N., & Volpert, O. V. (2004) · Molecular Cancer Research · doi:10.1158/1541-7786.541.2.10 · Cited by 69 · see citing works
TRAF6 Is Essential for Maintenance of Regulatory T Cells That Suppress Th2 Type Autoimmunity
Muto, G., Kotani, H., Kondo, T., Morita, R., Tsuruta, S., Kobayashi, T., Luche, H., Fehling, H. J., Walsh, M. C., Choi, Y., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074639 · Cited by 65 · cited 1× · see citing works
“TRAF6 deficiency leads to reduced expression and stability of Foxp3 and a rapid conversion of Foxp3+ Tregs to Foxp3 cells [63].”
Background
Orphan nuclear transcription factor TR3/Nur77 regulates microvessel permeability by targeting endothelial nitric oxide synthase and destabilizing endothelial junctions
Zhao, D., Qin, L., Bourbon, P.-M., James, L. W., Dvorak, H. F., & Zeng, H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018438108 · Cited by 60 · cited 1× · see citing works
“NR4A1 transcriptional activity has also been shown to regulate vascular permeability in vitro and in vivo by enhancing endothelial NO synthase and down-regulating several EC junction proteins that are required to maintain vascular homeostasis [65,66].”
Background
Identification of NR4A2 as a transcriptional activator of IL-8 expression in human inflammatory arthritis
Aherne, C. M., McMorrow, J. P., Kane, D. J., FitzGerald, O., Mix, K. S., & Murphy, E. P. (2009) · Molecular Immunology · doi:10.1016/j.molimm.2009.07.019 · Cited by 60 · cited 1× · see citing works
“and secretion by FLS is through a co-operative NR4A2/NF- B driven process [69,76].”
BackgroundSelf-citation
Nuclear Receptors Nur77 and Nurr1 Modulate Mesenchymal Stromal Cell Migration
Maijenburg, M. W., Gilissen, C., Melief, S. M., Kleijer, M., Weijer, K. C., ten Brinke, A., Roelofs, H., van Tiel, C. M., Veltman, J. A., de Vries, C. J. M., et al. (2011) · Stem Cells and Development · doi:10.1089/scd.2011.0076 · Cited by 59 · cited 1× · see citing works
“Such observations are supported by NR4A1 and NR4A2 gain of function experiments which reveal enhanced IL-6 and IL-8 production by bone marrow derived mesenchymal stromal cells [78].”
Background
Effect of nuclear factor-kappaB inhibition on rheumatoid fibroblast-like synoviocytes and collagen induced arthritis.
Okazaki, Y., Sawada, T., Nagatani, K., Komagata, Y., Inoue, T., Muto, S., Itai, A., & Yamamoto, K. (2005) · PubMed · Cited by 53 · see citing works
Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells
Crean, D., Cummins, E. P., Bahar, B., Mohan, H. M., McMorrow, J. P., & Murphy, E. P. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402039 · Cited by 52 · cited 1× · see citing works
“anti-neoplastic agent, 6-mercaptopurine, and related compounds including adenosine [35,46].”
BackgroundSelf-citation
NOR-1 modulates the inflammatory response of vascular smooth muscle cells by preventing NFκB activation
Calvayrac, O., Rodríguez‐Calvo, R., Martí-Pàmies, Í., Alonso, J., Ferrán, B., Aguiló, S., Crespo, J., Rodríguez‐Sinovas, A., Rodrı́guez, C., & Martínez‐González, J. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.12.015 · Cited by 51 · cited 2× · see citing works
“NR4A3 was shown to direct and limit the inflammatory response by inhibiting NF-kB/p65 activation, nuclear translocation and target gene expression [51].”
Background
VEGF stimulates PKD‐mediated CREB‐dependent orphan nuclear receptor Nurr1 expression: Role in VEGF‐induced angiogenesis
Zhao, D., Desai, S., & Zeng, H. (2010) · International Journal of Cancer · doi:10.1002/ijc.25600 · Cited by 48 · cited 1× · see citing works
“NR4A1 transcriptional activity is both necessary and sufficient for VEGF-A-Induced proliferation and survival of cultured endothelial cells (ECs) and for angiogenesis in vivo, while depletion of NR4A2 expression attenuates VEGF-A-induced endothelial proliferation, migration and in vivo matrigel angiogenesis [67,68].”
Background
NR4A receptors up-regulate the antiproteinase alpha-2 macroglobulin (A2M) and modulate MMP-2 and MMP-9 in vascular smooth muscle cells
Rodríguez‐Calvo, R., Ferrán, B., Alonso, J., Martí-Pàmies, Í., Aguiló, S., Calvayrac, O., Rodrı́guez, C., & Martínez‐González, J. (2015) · Thrombosis and Haemostasis · doi:10.1160/th14-07-0645 · Cited by 47 · see citing works
Over-expression of Neuron-derived Orphan Receptor-1 (NOR-1) exacerbates neointimal hyperplasia after vascular injury
Rodríguez‐Calvo, R., Guadall, A., Calvayrac, O., Navarro, M. A., Alonso, J., Ferrán, B., de Diego, A., Muniesa, P., Osada, J., Rodrı́guez, C., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt042 · Cited by 47 · cited 1× · see citing works
“Hence to clarify the role of NR4A3 in mediating the response of vascular smooth muscle cells to inflammatory stimuli, in vivo cell specific gain and loss of function studies have recently been undertaken [50,51].”
Background
Orphan nuclear receptor NR4A2 induces synoviocyte proliferation, invasion, and matrix metalloproteinase 13 transcription
Mix, K. S., McMahon, K., McMorrow, J. P., Walkenhorst, D. E., Smyth, A. M., Petrella, B. L., Gogarty, M., Fearon, U., Veale, D. J., Attur, M. G., et al. (2012) · Arthritis & Rheumatism · doi:10.1002/art.34399 · Cited by 44 · cited 1× · see citing works
“Enhanced NR4A2 activity induces a phenotypic shift in normal FLS that parallels the cellular transformation and hyperplasia observed during the progression of inflammatory arthritis [75].”
BackgroundSelf-citation
The neuron-derived orphan receptor 1 (NOR1) is induced upon human alternative macrophage polarization and stimulates the expression of markers of the M2 phenotype
Paoli, F. D., Eeckhoute, J., Copin, C., Vanhoutte, J., Duhem, C., Derudas, B., Dubois‐Chevalier, J., Colin, S., Zawadzki, C., Jude, B., et al. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.04.798 · Cited by 43 · see citing works
The Nuclear Receptor Nr4a1 Controls CD8 T Cell Development Through Transcriptional Suppression of Runx3
Nowyhed, H. N., Huynh, T. R., Blatchley, A., Wu, R., Thomas, G. D., & Hedrick, C. C. (2015) · Scientific Reports · doi:10.1038/srep09059 · Cited by 42 · cited 1× · see citing works
“The authors reveal during CD8+ T cell development NR4A1 recruits the co-repressor CoREST complex, binds to a distal promoter region of the Runx3 gene, and subsequent gene repression [62].”
Background
Tumor Necrosis Factor Inhibition Modulates Thrombospondin-1 Expression in Human Inflammatory Joint Disease through Altered NR4A2 Activity
McMorrow, J. P., Crean, D., Gogarty, M., Smyth, A. M., Connolly, M., Cummins, E. P., Veale, D. J., Fearon, U., Tak, P. P., FitzGerald, O., et al. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.06.029 · Cited by 41 · cited 4× · see citing works
“NR4A2 functions as a transcriptional repressor of TSP-1 in human synovial tissue leading to reduced TSP-1 expression [69].”
BackgroundInfluentialSelf-citation
Orphan nuclear receptor TR3/Nur77 improves wound healing by upregulating the expression of integrin β4
Niu, G., Ye, T., Qin, L., Bourbon, P. M., Chang, C., Zhao, S., Li, Y., Zhou, L., Cui, P., Rabinovitz, I., et al. (2014) · The FASEB Journal · doi:10.1096/fj.14-257550 · Cited by 39 · see citing works
Deficiency of the NR4A Orphan Nuclear Receptor NOR1 in Hematopoietic Stem Cells Accelerates Atherosclerosis
青华, Liu, Y., Zhao, Y., Aono, J., Jones, K. L., Heywood, E. B., Howatt, D. A., Friday, C. M., Daugherty, A., Liang, Y., et al. (2014) · Stem Cells · doi:10.1002/stem.1747 · Cited by 33 · see citing works
Limited Role of Nuclear Receptor Nur77 in Escherichia coli-Induced Peritonitis
Hamers, A. A. J., Uleman, S., van Tiel, C. M., Kruijswijk, D., van Stalborch, A.-M. D., Huveneers, S., de Vries, C. J. M., & Veer, C. V. ′. (2013) · Infection and Immunity · doi:10.1128/iai.00721-13 · Cited by 20 · cited 1× · see citing works
“NR4A1 transcriptional activity has also been shown to regulate vascular permeability in vitro and in vivo by enhancing endothelial NO synthase and down-regulating several EC junction proteins that are required to maintain vascular homeostasis [65,66].”
Background
T cell-specific inhibition of multiple apoptotic pathways blocks negative selection and causes autoimmunity
Burger, M. L., Leung, K. K., Bennett, M. J., & Winoto, A. (2014) · eLife · doi:10.7554/elife.03468 · Cited by 20 · see citing works

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PPARγ agonist pioglitazone reverses pulmonary hypertension and prevents right heart failure via fatty acid oxidation
Legchenko, E., Chouvarine, P., Borchert, P., Fernandez‐Gonzalez, A., Snay, E. R., Meier, M., Maegel, L., Mitsialis, S. A., Rog‐Zielinska, E. A., Kourembanas, S., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aao0303 · Cited by 295 · see citing works
Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases
Cronstein, B. N., & Sitkovsky, M. V. (2016) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2016.178 · Cited by 258 · see citing works
Stroke–Heart Syndrome: Recent Advances and Challenges
Scheitz, J. F., Sposato, L. A., Schulz‐Menger, J., Nolte, C. H., Backs, J., & Endres, M. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.122.026528 · Cited by 190 · see citing works
Immunology of IL-12: An update on functional activities and implications for disease
Ullrich, K. A.-M., Schulze, L. L., Paap, E.-M., Müller, T. M., Neurath, M. F., & Zundler, S. (2020) · EXCLI journal · doi:10.17179/excli2020-3104 · Cited by 137 · see citing works
“Sinomenine, an alkaloid extracted from the Chinese medical plant Sinomenium acutum, which is approved in China, suppressed RA progression by regulating the secretion of several inflammatory cytokines, such as IL-12p40, IL-6, TNF-α (Liu et al., 2018).”
BackgroundInfluential
Targeting NR4A Nuclear Receptors to Control Stromal Cell Inflammation, Metabolism, Angiogenesis, and Tumorigenesis
Crean, D., & Murphy, E. P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.589770 · Cited by 86 · see citing works
“The COX-2/PGE2/NR4A signaling findings complement previous studies where NR4A has been shown to be a regulator of stromal and immune cell functions (Murphy and Crean, 2015) and linked to the expression of prolactin expression in inflammatory joint disease (McCoy et al.”
BackgroundSelf-citation
Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes
Chiarelli, N., Ritelli, M., Zoppi, N., & Colombi, M. (2019) · Genes · doi:10.3390/genes10080609 · Cited by 82 · see citing works
Transcriptome-Wide Expression Profiling in Skin Fibroblasts of Patients with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type
Chiarelli, N., Carini, G., Zoppi, N., Dordoni, C., Ritelli, M., Venturini, M., Castori, M., & Colombi, M. (2016) · PLOS ONE · doi:10.1371/journal.pone.0161347 · Cited by 78 · see citing works
“NR4A1, NR4A2, and NR4A3 are ligand-dependent transcription factors that modulate NF-kB activity in a dynamic fashion, either repressing or enhancing target gene expression leading to altered inflammatory outcome [59].”
Background
NR4A1 and NR4A3 restrict HSC proliferation via reciprocal regulation of C/EBPα and inflammatory signaling
Freire, P. R., & Conneely, O. M. (2018) · Blood · doi:10.1182/blood-2017-07-795757 · Cited by 70 · see citing works
Compensatory Expression of Nur77 and Nurr1 Regulates NF-κB–Dependent Inflammatory Signaling in Astrocytes
Popichak, K. A., Hammond, S. L., Moreno, J. A., Afzali, M. F., Backos, D. S., Slayden, R. D., Safe, S., & Tjalkens, R. (2018) · Molecular Pharmacology · doi:10.1124/mol.118.112631 · Cited by 53 · see citing works
“Discussion Neuronal cell death is accompanied by activation of microglia and astrocytes, resulting in the coordinated expression of multiple NF-kB–regulated inflammatory genes (Verkhratsky and Butt, 2007; Béchade et al., 2014; Murphy and Crean, 2015).”
BackgroundResultInfluential
Role of MiRNAs in Inflammatory Bowel Disease
Cao, B., Xin Min, Z. H. O. U., Ma, J., Zhou, W. P., Yang, W., Fan, D., & Hong, L. (2017) · Digestive Diseases and Sciences · doi:10.1007/s10620-017-4567-1 · Cited by 53 · see citing works
Nur77 attenuates endothelin-1 expression via downregulation of NF-κB and p38 MAPK in A549 cells and in an ARDS rat model
Jiang, Y., Zeng, Y. A., Huang, X., Qin, Y., Luo, W., Xiang, S., Sooranna, S. R., & Pinhu, L. (2016) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00043.2016 · Cited by 52 · see citing works
Cedrol attenuates collagen-induced arthritis in mice and modulates the inflammatory response in LPS-mediated fibroblast-like synoviocytes
Chen, X., Shen, J. F., Zhao, J.-M., Guan, J., Li, W., Xie, Q.-M., & Zhao, Y. (2020) · Food & Function · doi:10.1039/d0fo00549e · Cited by 47 · see citing works
NR4A Receptors Differentially Regulate NF-κB Signaling in Myeloid Cells
McEvoy, C. M., de Gaetano, M., Giffney, H. E., Bahar, B., Cummins, E. P., Brennan, E. P., Barry, M. C., Belton, O., Godson, C., Murphy, E. P., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00007 · Cited by 44 · see citing works
“…by acting as feedback regulators of NF-κ B signaling, and more recently have been identified as promoters of inflammatory resolution processes (1–3, 7 ) NR4A receptors have profound effects on NF-κ B, paradoxically repressing or enhancing its activity depending on tissue, cell type, or disease…”
BackgroundSelf-citation
Probing the links: Long non-coding RNAs and NF-κB signalling in atherosclerosis
Hussain, M. S., Afzal, O., Gupta, G., Altamimi, A. S. A., Almalki, W. H., Alzarea, S. I., Kazmi, I. A., Kukreti, N., Gupta, S. K., Sulakhiya, K., et al. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.154773 · Cited by 43 · see citing works
Effects of miR-33 Deficiency on Metabolic and Cardiovascular Diseases: Implications for Therapeutic Intervention
Ortega, R., Liu, B., & Persaud, S. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310777 · Cited by 41 · see citing works
NR4A1 regulates cerebral ischemia-induced brain injury by regulating neuroinflammation through interaction with NF-κB/p65
Zhang, Y.-J., Song, J.-R., & Zhao, M. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.08.008 · Cited by 39 · see citing works
Transcriptional modulation of regulatory T cell development by novel regulators NR4As
Won, H. Y., & Hwang, E. S. (2016) · Archives of Pharmacal Research · doi:10.1007/s12272-016-0803-z · Cited by 38 · see citing works
SPDEF suppresses head and neck squamous cell carcinoma progression by transcriptionally activating NR4A1
Wang, Y., Ren, X., Li, W., Cao, R., Liu, S., Jiang, L., Cheng, B., & Xia, J. (2021) · International Journal of Oral Science · doi:10.1038/s41368-021-00138-0 · Cited by 37 · see citing works
Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis
Salnikova, D. I., Nikiforov, N. G., Postnov, A. Y., & Orekhov, A. N. (2024) · Diseases · doi:10.3390/diseases12050081 · Cited by 33 · see citing works
“This statement is confirmed by the NF-kB participation in the production of macrophage inflammatory protein-1a and the chemokine IL-8 [65].”
Background
Nuclear Receptor Nur77 Deficiency Alters Dendritic Cell Function
Karthaus, N., Kers‐Rebel, E. D., Looman, M. W. G., Ichinose, H., de Vries, C. J. M., & Ansems, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01797 · Cited by 33 · see citing works
“As NR4A family members have been reported to crosstalk with the NF-κB pathway (54), we investigated whether the enhanced cytokine production was dependent on NF-κB signaling.”
BackgroundInfluential
The Footprints of Poly-Autoimmunity: Evidence for Common Biological Factors Involved in Multiple Sclerosis and Hashimoto’s Thyroiditis
Perga, S., Martire, S., Montarolo, F., Giordani, I., Spadaro, M., Bono, G., Corvisieri, S., Messuti, I., Panzica, G., Orlandi, F., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00311 · Cited by 32 · see citing works
“TNFAIP3 and the NR4A family, including NR4A1, NR4A2, and NR4A3, represent a group of potent inhibitors of NF-kB pathway (56, 57), whose deregulation has been associated to several chronic inflammatory and autoimmune conditions including MS (58, 59).”
Background
The Association Between Polycystic Ovary Syndrome and Its Dermatological Manifestations
Sekhon, A. K., Zergham, A. S., Tserenpil, G., Mebasher, A., & Malik, B. H. (2020) · Cureus · doi:10.7759/cureus.6855 · Cited by 30 · see citing works
Ginkgolide B attenuates collagen-induced rheumatoid arthritis and regulates fibroblast-like synoviocytes-mediated apoptosis and inflammation
Xie, C., Jiang, J., Liu, J., Yuan, G., & Zhao, Z. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-6420 · Cited by 30 · see citing works
“Studies have shown that NF-κB/ p65 plays a key role in the transcription of inflammatory cytokines and chemokines (36).”
Background
Treatment with the NR4A1 agonist cytosporone B controls influenza virus infection and improves pulmonary function in infected mice
Egarnes, B., Blanchet, M., & Gosselin, J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186639 · Cited by 29 · see citing works
Role of nutraceutical against exposure to pesticide residues: power of bioactive compounds
Sajad, M., Shabir, S., Singh, S. K., Bhardwaj, R., Alsanie, W. F., Alamri, A. S., Alhomrani, M., Alsharif, A., Vamanu, E., & Singh, M. P. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1342881 · Cited by 27 · see citing works
Oncogenic Orphan Nuclear Receptor NR4A3 Interacts and Cooperates with MYB in Acinic Cell Carcinoma
Lee, D. Y., Brayer, K. J., Mitani, Y., Burns, E. A., Rao, P. H., Bell, D., Williams, M. D., Ferrarotto, R., Pytynia, K. B., El‐Naggar, A. K., et al. (2020) · Cancers · doi:10.3390/cancers12092433 · Cited by 27 · see citing works
“Critical cellular pathways, including the NFKappaB [34] and Wnt signaling [35,36] have been reported to be the targets of the NR4A family member activation.”
Background
Immune imbalance of global gene expression, and cytokine, chemokine and selectin levels in the brains of offspring with social deficits via maternal immune activation
Hsueh, P., Lin, H., Wang, H. ‐., Liu, C., Ni, W.-F., Liu, J. ‐., Chang, H., Sun, D., Chen, Y. ‐., & Chen, Y. (2018) · Genes Brain & Behavior · doi:10.1111/gbb.12479 · Cited by 27 · see citing works
“The nr4a1 gene is an early gene that inhibits the inflammatory nuclear factor-kappa B pathway and suppresses the production of chronically inflamed cells in patients with atherosclerosis, arthritis, colitis or psoriasis.(50) The upregulation of nr4a1 expression has been observed in mice that display anxiety-related be…”
Background
The Impact of Aging on the Lung Alveolar Environment, Predetermining Susceptibility to Respiratory Infections
Torrelles, J. B., Restrepo, B. I., Bai, Y., Ross, C. N., Schlesinger, L. S., & Turner, J. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.818700 · Cited by 23 · see citing works
“Nuclear receptors (NRs) function as cellular transcription factors enabling macrophages and other myeloid cells to sense their local environment and shape their immune and metabolic responses (Murphy and Crean, 2015; LeopoldWager et al., 2019a; Bichiou et al., 2021).”
Background
Nur77 and PPARγ regulate transcription and polarization in distinct subsets of M2-like reparative macrophages during regenerative inflammation
Garabuczi, É., Tarban, N., Fige, É., Patsalos, A., Halász, L., Szendi-Szatmári, T., Sarang, Z., Király, R., & Szondy, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1139204 · Cited by 22 · see citing works
“This effect of Nur77 is mediated partly by controlling the mitochondrial metabolism (45), but also by interfering with the NF-kB-mediated proinflammatory signaling (19).”
Background
Advancements in rheumatoid arthritis therapy: a journey from conventional therapy to precision medicine via nanoparticles targeting immune cells
Laha, A., Nasra, S., Bhatia, D. D., & Kumar, A. (2024) · Nanoscale · doi:10.1039/d4nr02182g · Cited by 21 · see citing works
NR4A1-3 nuclear receptor activity and immune cell dysregulation in rheumatic diseases
Murphy, E. P., & Crean, D. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.874182 · Cited by 18 · see citing works
“Consistent with findings that NR4A2 is expressed by macrophage cells in RA ST and in several models of murine autoimmune joint disease, treatment of monocyte and macrophage cells with diverse mediators including lipopolysaccharide (LPS), cytokines, growth factors or oxidized lipids triggers the transcriptional inducti…”
BackgroundSelf-citation
IGF2-NR4A2 Signaling Regulates Macrophage Subtypes to Attenuate Liver Cirrhosis
Yao, L., Hu, X., Yuan, M., Zhang, Q., Liu, P., Yang, L., Dai, K., & Jiang, Y. (2023) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2022.00392 · Cited by 15 · see citing works
Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma
Acevedo, N., Ezer, S., Merid, S. K., Gaertner, V. D., Söderhäll, C., D’Amato, M., Kabesch, M., Melén, E., Kere, J., & Pulkkinen, V. (2017) · PLoS ONE · doi:10.1371/journal.pone.0176568 · Cited by 16 · see citing works
Nur77 downregulation triggers pulmonary artery smooth muscle cell proliferation and migration in mice with hypoxic pulmonary hypertension via the Axin2-β-catenin signaling pathway
Nie, X., Tan, J., Dai, Y., Mao, W., Chen, Y., Qin, G., Li, G., Shen, C., Zhao, J., & Chen, J. (2016) · Vascular Pharmacology · doi:10.1016/j.vph.2016.11.002 · Cited by 16 · see citing works
The NR4A agonist, Cytosporone B, attenuates pro-inflammatory mediators in human colorectal cancer tissue ex vivo
Ismaiel, M., Murphy, B. P., Aldhafiri, S., Giffney, H. E., Thornton, K. H., Mukhopadhya, A., Keogh, C. E., Fattah, S., Mohan, H. M., Cummins, E. P., et al. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.03.110 · Cited by 13 · see citing works
Self-citation
Ftz-F1H promotes white spot syndrome virus infection in shrimp by suppressing the Dorsal pathway
Weng, K., Zuo, H., Zhu, Z., Guo, Z., Weng, S., He, J., & Xu, X. (2021) · Aquaculture · doi:10.1016/j.aquaculture.2021.737708 · Cited by 13 · see citing works
Upregulation of NOR-1 in calcified human vascular tissues: impact on osteogenic differentiation and calcification
Ballester‐Servera, C., Cañes, L., Alonso, J., Puertas-Umbert, L., Vázquez-Sufuentes, P., Taurón, M., Roselló-Díez, E., Marín, F. R., Rodrı́guez, C., & Martínez‐González, J. (2023) · Translational research · doi:10.1016/j.trsl.2023.09.004 · Cited by 11 · see citing works
Single-cell and bulk RNA sequencing highlights the role of M1-like infiltrating macrophages in antibody-mediated rejection after kidney transplantation
Pang, Q., Chen, L., An, C., Zhou, J., & Xiao, H. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e27865 · Cited by 11 · see citing works
“Macrophage NR4A1-3 receptors can integrate as well as limit inflammatory signaling, and promote tissue repair [48].”
Background
Molecular genetic response to varied wavelengths of light in Xiphophorus maculatus skin
Chang, J. T., Lü, Y., Boswell, W. T., Boswell, M., Caballero, K. L., & Walter, R. B. (2015) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2015.10.002 · Cited by 11 · see citing works
“…to lipids, many were involved in transcriptional regulation of processes such as inflammatory response (e.g. ankrd1a and nr4a3; Liu et al., 2015; Murphy and Crean, 2015), lipid regulation (e.g. abca1b and srebf1; Oram and Lawn, 2001; Eberlé et al., 2004), and muscle protein ubiquitination (e.g.…”
Background
New lathyrane diterpenoids with anti-inflammatory activity isolated from the roots of Jatropha curcas L
Huang, J.-D., Zhang, C., WenJuan, X., Lian, C., Liu, X., Wang, C., & Liu, J. (2020) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.113673 · Cited by 11 · see citing works
Transcription cofactor GRIP1 differentially affects myeloid cell–driven neuroinflammation and response to IFN-β therapy
Mimouna, S., Rollins, D. A., Shibu, G., Tharmalingam, B., Deochand, D. K., Chen, X., Oliver, D., Chinenov, Y. V., & Rogatsky, I. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20192386 · Cited by 10 · see citing works
“Nr4a receptors in turn control their target genes by binding either to a specific octamer DNA sequence known as the NGFI-B response element as monomers or to palindromic sequences termed the Nur response element as homo- or heterodimers and activating or repressing transcription (Kurakula et al., 2014; Murphy and Crea…”
Background
Roles and Mechanisms of miRNAs in Abdominal Aortic Aneurysm: Signaling Pathways and Clinical Insights
Zhang, H., Zhang, K.-Y., Gu, Y.-R., Tu, Y., & Ouyang, C. (2024) · Current Atherosclerosis Reports · doi:10.1007/s11883-024-01204-8 · Cited by 9 · see citing works
“Afterwards, nuclear receptor 4A (NR4A) was down-regulated, and inflammatory responses were elevated through the activation of NF-κB signaling pathway [17, 18].”
Loss of Nr4a1 ameliorates endothelial cell injury and vascular leakage in lung transplantation from circulatory-death donor
Kawana, S., Okazaki, M., Sakaue, T., Hashimoto, K., Nakata, K., Choshi, H., Tanaka, S., Miyoshi, K., Ohtani, S., Ohara, T., et al. (2024) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2024.09.028 · Cited by 9 · see citing works
Regulation of NR4A2 Gene Expression and Its Importance in Neurodegenerative and Psychiatric Diseases
Ruiz-Sánchez, E., Rojas, C., Gómez, P. Y., Martínez‐Rodríguez, N., Ruíz-Chow, Á. A., Nava-Ruíz, C., Ibáñez-Cervantes, G., Arciniega-Martínez, I. M., Reséndiz‐Albor, A. A., & Rojas, P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26189162 · Cited by 9 · see citing works
“The binding of CREB and NF-κ B to the NR4A2 promoter region is not constant, but both TFs regulate NR4A2 expression in a cell, tissue-and time-specific manner [27,71].”
Influential
Variability in Behavioral Phenotypes after Forced Swimming-Induced Stress in Rats Is Associated with Expression of the Glucocorticoid Receptor, Nurr1, and IL-1β in the Hippocampus
Ruiz-Sánchez, E., López-Ramírez, A. M., Ruíz-Chow, Á. A., Calvillo, M., Reséndiz‐Albor, A. A., Anguiano, B., & Rojas, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312700 · Cited by 9 · see citing works
“It is known that Nurr1 senses and increases rapidly in response to such stimuli [25,26].”
Background
The impact of pre-freezing storage time and temperature on gene expression of blood collected in EDTA tubes
Martire, S., Valentino, P., Marnetto, F., Mirabile, L., Capobianco, M. A. N., & Bertolotto, A. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07320-5 · Cited by 8 · see citing works
Global Transcriptomic Analysis of the Canine corpus luteum (CL) During the First Half of Diestrus and Changes Induced by in vivo Inhibition of Prostaglandin Synthase 2 (PTGS2/COX2)
Pereira, M. T., Graubner, F. R., Rehrauer, H., Janowski, T. E., Hoffmann, B., Boos, A., & Kowalewski, M. P. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00715 · Cited by 8 · see citing works
Insights into the Signal Transduction Pathways of Mouse Lung Type II Cells Revealed by Transcription Factor Profiling in the Transcriptome
Ramana, C. V. (2019) · Genomics & Informatics · doi:10.5808/gi.2019.17.1.e8 · Cited by 7 · see citing works
Opposite effects of acute and chronic amphetamine on Nurr1 and NF-κB p65 in the rat ventral tegmental area
Arredondo, C., González, M., Andrés, M. E., & Gysling, K. (2016) · Brain Research · doi:10.1016/j.brainres.2016.09.031 · Cited by 7 · see citing works
“As well, the other Nur family members: Nur77 and Nor-1 have common pathways with p65 in several cell types (Hong et al., 2004; Calvayrac el al., 2015; Murphy and Crean, 2015), showing that Nur and NF-B are closely related in different cell phenotypes.”
Pterocarpus santalinus Selectively Inhibits a Subset of Pro-Inflammatory Genes in Interleukin-1 Stimulated Endothelial Cells
Natalia, P., Zwirchmayr, J., Rudžionytė, I., Pulsinger, A., Breuss, J. M., Uhrín, P., Rollinger, J. M., & de Martin, R. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.802153 · Cited by 6 · see citing works
“NR4As have been shown to cross-talk with NF-κB and thereby modulate its activity (Murphy and Crean, 2015).”
Background
NR4A1 Acts as a Nutrient Sensor That Inhibits the Effects of Aging
Safe, S. H. (2025) · Nutrients · doi:10.3390/nu17162709 · Cited by 6 · see citing works
OTUB2/NR4A1 restrains the development of preeclampsia by suppressing macrophage M1 polarization
Wang, Y., Wang, Y., Tong, F., Gao, Q., Li, B., & Zhao, Y. (2025) · Communications Biology · doi:10.1038/s42003-025-08755-9 · Cited by 6 · see citing works
El receptor nuclear NOR-1 (Neuron-derived Orphan Receptor-1) en el remodelado vascular patológico
Ballester‐Servera, C., Cañes, L., Alonso, J., Puertas-Umbert, L., Taurón, M., Rodrı́guez, C., & Martínez‐González, J. (2022) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/j.arteri.2022.03.002 · Cited by 5 · see citing works
A Nuclear Attack on Thrombosis and Inflammation
Conway, E. M. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.115.306979 · Cited by 5 · see citing works
Nuclear receptor 4A1 (NR4A1) upregulated by n ‐butylidenephthalide via the mitogen‐activated protein kinase ( MAPK) pathway ameliorates drug‐induced gingival enlargement
Ueda, T., Matsuda, S., Ninomiya, Y., Nakashima, F., Yasuda, K., Furutama, D., Memida, T., Yoshimoto, T., Kajiya, M., Ohta, K., et al. (2024) · BioFactors · doi:10.1002/biof.2077 · Cited by 4 · see citing works
“37 Taken together, our results suggest that BP may suppress inflammation in gingival tissue in DIGE directly or indirectly through NR4A1 upregulation.”
Subcellular Localization of NR4A2 Orphan Nuclear Receptor Expression in Human and Mouse Synovial Joint Tissue
Smyth, A. M., Gogarty, M., Crean, D., & Murphy, E. P. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9195-2_3 · Cited by 4 · see citing works
Self-citation
Intrapulmonary-administered myeloid derived suppressor cells rescue mice from Pseudomonas aeruginosa infection and promote a regulatory/repair phenotype
Born-Bony, M., Cornu, C., Villeret, B., Gratio, V., Voulhoux, R., & Sallenave, J. (2025) · Mucosal Immunology · doi:10.1016/j.mucimm.2025.03.001 · Cited by 3 · see citing works
Local Regulation of Adrenal Steroidogenesis: Subtle in vitro Effects of IL-1β on the Human Cell Line NCI-H295R Steroid Production along with Changes in MicroRNA Profile and Orphan Nuclear Receptors NR4As
Santucci, N. E., Stampone, R., da Silva, E. B. F., Villar, S. R., Spinelli, S. V., Linhares‐Lacerda, L., Alves, M. R., Bay, M. L., & Bottasso, O. A. (2020) · NeuroImmunoModulation · doi:10.1159/000512325 · Cited by 3 · see citing works
A narrative review on bridging the gap between periodontitis and cardiovascular disease: exploring the cellular and molecular mechanisms of periodontitis-driven atherosclerosis
Kumar, R., Dhanasekaran, A., & Venugopal, P. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10806-7 · Cited by 2 · see citing works
Integrative multi-omics analysis reveals gut-skin axis mechanisms and novel therapeutic target GALE in atopic dermatitis
Cao, F., Liu, A., Tong, J., Guo, C. X., Zhang, H., Pang, Y., Tang, K., Yu, Q., & Guo, J. (2025) · mSystems · doi:10.1128/msystems.01403-25 · Cited by 2 · see citing works
Identification and Analysis of Potential Biomarkers Associated with Neutrophil Extracellular Traps in Cervicitis
Liang, W., Bai, Y., Zhang, H., Mo, Y., Li, X., Huang, J., Lei, Y., Gao, F., Dong, M., Li, S., et al. (2024) · Biochemical Genetics · doi:10.1007/s10528-024-10919-x · Cited by 2 · see citing works
“Immune cell polarization is fundamental in directing distinct phases of inflammation (Murphy and Crean 2015).”
Crosstalk between CLL and cutaneous T-cell lymphoma: MIF-CD74 axis and dysregulated inflammatory signaling
Yin, M., Srinivas, N., Lei, K. C., Murad, M., Ugurel, S., Livingstone, E., Hyun, J., Gambichler, T., Rached, N. A., & Becker, J. C. (2025) · EJC Skin Cancer · doi:10.1016/j.ejcskn.2025.100735 · Cited by 2 · see citing works
Protein kinase D, ubiquitin and proteasome pathways are involved in adenosine receptor-stimulated NR4A expression in myeloid cells
Giffney, H. E., Cummins, E. P., Murphy, E. P., Brayden, D. J., & Crean, D. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.03.082 · Cited by 2 · see citing works
Self-citation
Correction: Transcription cofactor GRIP1 differentially affects myeloid cell–driven neuroinflammation and response to IFN-β therapy
Mimouna, S., Rollins, D. A., Shibu, G., Tharmalingam, B., Deochand, D. K., Chen, X., Oliver, D., Chinenov, Y. V., & Rogatsky, I. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.2019238611162020c · Cited by 3 · see citing works
The Role of NF-κB p65 in White Tea Aqueous Extract-Induced Cancer Cell Apoptosis
Liu, L., Qin, L., Zhang, W., Wen, M., Zheng, S., & Ye, Z. (2023) · American Journal of Plant Sciences · doi:10.4236/ajps.2023.143018 · Cited by 1 · see citing works
NR4A Receptors in Immunity: Bridging Neuroendocrine and Inflammatory Pathways
Santucci, N. E., & Ferreira, S. (2025) · Receptors · doi:10.3390/receptors5010003 · Cited by 1 · see citing works
“While structurally similar, the N-terminal domain shows only 26–28% sequence homology among NR4A members, yet it is critical for transcriptional regulation, post-translational modifications, and functional diversification [10,12,13].”
Influential
Oxytocin Modulates Microglial IL-17-Linked Inflammatory Pathways Through the IL-6/COX-2
Hwang, W., Jang, Y. H., Hong, J., Kang, S., Hur, J. K., & Lee, H. J. (2026) · Life · doi:10.3390/life16010105 · Cited by 1 · see citing works
Isoginkgetin stabilizes atherosclerotic plaques by targeting NR4A2 to modulate the PPAR signaling pathway and reprogram ceramide metabolism, thereby inhibiting vascular smooth muscle cell phenotypic transformation
Wei, D., Zhong, Z., Li, H., Qi, J., Liu, Y., Cao, H., Ma, Y., Li, Z., Yang, G., Jiang, Y., et al. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116993 · Cited by 1 · see citing works
Differential inflammatory profile of mesenteric and omental fat in patients with colorectal cancer
Ismaiel, M., Murphy, B. P., Hayes, C., O’Connell, L., & Winter, D. C. (2021) · British journal of surgery · doi:10.1093/bjs/znab300 · Cited by 1 · see citing works
Effects of Selected Non-biological and Biological Disease-Modifying Anti-rheumatic Drugs, and mRNA Vaccines on Mononuclear Phagocyte System
Dráfi, F., Poništ, S., Sepodes, B. M. N., & Bauerová, K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00110-9 · Cited by 1 · see citing works
Inflammation in the Pathogenesis of Rheumatoid Arthritis and in Experimental Arthritis: Evaluation of Combinations of Carnosic Acid and Extract ofRhodiola roseaL. with Methotrexate
Poništ, S., Pružinská, K., & Bauerová, K. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.99073
Nuclear receptor NOR-1 (Neuron-derived Orphan Receptor-1) in pathological vascular remodelling
Ballester‐Servera, C., Cañes, L., Alonso, J., Puertas-Umbert, L., Taurón, M., Rodrı́guez, C., & Martínez‐González, J. (2022) · Clínica e Investigación en Arteriosclerosis (English Edition) · doi:10.1016/j.artere.2022.06.008
Regulation of polarization of lung macrophages by Nur77/Nr4a1
Karikalan, B., Chakravarthi, S., & Li, J. (2023) · IP Archives of Cytology and Histopathology Research · doi:10.18231/j.achr.2023.021
Transcriptional response of macrophages to combined stimulation of NOD-like and Toll-like receptors (report 2)
Михайловна, М. А., & Pashenkov, M. V. (2023) · Immunologiya · doi:10.33029/1816-2134-2023-44-5-534-544
The NR4A Orphan Receptor Modulator C-DIM12 Selectively Alters Inflammatory Mediators in Myeloid Cells
Aldhafiri, S., Marai, M., Ismaiel, M., Murphy, B. P., Giffney, H. E., Hall, T. J., Murphy, E. P., Cummins, E. P., & Crean, D. (2023) · Receptors · doi:10.3390/receptors2040018
“Additionally, NR4As are known to be key players in inflammatory disease and key regulators of myeloid cell function [2,6–8].”
BackgroundSelf-citation
Expanding the Clinical Spectrum of NR4A2 ‐Related Disorder: A Systematic Literature Review and Case Series
Borden, C., Nasir, M. B., Roberts, M., Palange, L., & Wang, X. (2025) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.64145
“While in some contexts, NR4A2 promotes inflammation, in others it functions as a negative feedback regulator of the inflammatory cascade (McEvoy et al. 2002, 2017; Mahajan et al. 2015; Murphy and Crean 2015; Lilley et al. 2022).”
Childhood adversity and increased cytokine release from peripheral mononuclear cells of CHD patients – a pilot study
Wiche, H., Anhuef, O., Martinache, S., Simon, J. J., Frey, N., Backs, J., Friederich, H.-C., Schultz, J.-H., & Bruns, B. (2026) · BMC Cardiovascular Disorders · doi:10.1186/s12872-026-05713-z
“In this regard, NR4A3 has been shown to inhibit inflammation by NF-kB suppression [44, 45].”
An integrated computational framework for assessing toxicity mechanisms of benzo[a]pyrene diol epoxide-induced interstitial lung disease
Xiong, K., Huang, Y., Gao, C., Yu, S., Peng, M., Ji, M., & Shen, J. (2026) · Toxicology Research · doi:10.1093/toxres/tfag032
Differential Expression Profiles of Orphan Nuclear Receptors (NR4A) and N-myc Downstream-Regulated Gene Family (NDRG) in Patients with Inflammatory Bowel Disease
Fonseca‐Camarillo, G., Furuzawa‐Carballeda, J., Aguilar‐León, D., Barreto‐Zúñiga, R., Martínez‐Benítez, B., & Yamamoto-Furusho, J. K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27114769
“Although no endogenous ligands have been identified for NR4A receptors, pharmacological agents such as 6‑mercaptopurine or derivatives of bis(indolyl)methane can effectively modulate their activity [11,15–17].”
Pre-existing antibodies predict protection while mucosal inflammation correlates with symptomatic Bordetella pertussis infectionPreprint
Willemsen, L., Ren, Z., Shinde, P. S., Thrupp, N., Lee, J., Gupta, A., Sutherland, A., Orfield, S., Kojima, M., Azhan, A., et al. (2026) · medRxiv · doi:10.64898/2026.06.26.26356067
PROTAC-mediated targeting of IKKβ and NR4A1 for AML therapy
Maharjan, C. K., Liu, Y., Xiao, Y., Podder, B. R., Montgomery, T., Wang, L., Kim, M., Jin, Z., Anvar, S., Tithi, T. I., et al. (2026) · Oncogene · doi:10.1038/s41388-026-03925-3
FABP5 regulates an immunosuppressive microenvironment in hepatocellular carcinoma through the NF-κB/PD-L1 axis
安瑞, Hou, S., Hong, M., Zhen, J., Wang, Z., Huang, H., Zhao, W., Liao, M., Yuan, W., & Huang, D. (2026) · PLoS ONE · doi:10.1371/journal.pone.0356359

Review Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-B Are Required for Appropriate Inflammatory Responses and Immune Cell Homeostasis
Murphy, E. P., & Crean, D. (2016)
Self-citation
NR4A Receptors Differentially Regulate NF-κB Signaling in Myeloid Cells
McEvoy, C. M., de Gaetano, M., Giffney, H. E., Bahar, B., Cummins, E. P., Brennan, E. P., Barry, M. C., Belton, O., Godson, C., Murphy, E. P., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00007 · Cited by 44 · see citing works
Self-citation
Inflammation: a role for NR4A orphan nuclear receptors?
McMorrow, J. P., & Murphy, E. P. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390688 · Cited by 167 · see citing works
Self-citation
NF-κB in monocytes and macrophages – an inflammatory master regulator in multitalented immune cells
Mußbacher, M., Derler, M., Basílio, J., & Schmid, J. A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1134661 · Cited by 326 · see citing works
Nuclear factor kappa-B: The El Dorado of inflammatory immune response
Mukherjee, S., Dutta, S., Pati, S., Sarkar, T., Paul, S., Chakraborty, S., Basak, U., Dhar, S., Das, T., & Sa, G. (2024) · Journal of Cellular and Molecular Immunology · doi:10.46439/immunol.3.025 · Cited by 9 · see citing works

Authors: Murphy, E., & Crean, D.
Affiliations: University College Dublin (IE)
Corresponding author: Crean, Daniel
ORCID: Murphy, Evelyn
Crean, Daniel
Venue: Biomolecules
Publisher: MDPI AG
Published: 2015-06-29
Volume: 5
Issue: 3
Pages: 1302-1318
ISSN: 2218-273X (ISSN-L)
DOI: 10.3390/biom5031302
PMC: PMC4598753
OpenAlex: W2101559719
Cited by: 82
References: 81
Citations by year: 2026: 8 · 2025: 9 · 2024: 8 · 2023: 9 · 2022: 7 · 2021: 9 · 2020: 9 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 1
FWCI: 0.72
Type: journal article
Language: en
Open access: gold
dx.doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Biomolecules (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Science Foundation Ireland
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: NF-κB, transcriptional crosstalk, immune cell polarization, inflammation, immune cell homeostasis, monocytes, macrophages, T cells, endothelial cells, mesenchymal cells, chronic inflammation, hyperinflammation, therapeutic target
MeSH terms: Animals, Homeostasis, Humans, Immunity, Inflammation, Protein Binding, NF-kappa B, Orphan Nuclear Receptors

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Molecular Interactions between NR4A Orphan Nuclear Receptors and NF-κB Are Required for Appropriate Inflammatory Responses and Immune Cell Homeostasis

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