P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis
Open accessAbstract
Sepsis is characterized by a systemic inflammatory response followed by immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection.
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P2X7 receptor modulates acute and chronic infection, inflammatory diseases, sepsis, neuropathic pain, and T-cell activation.
“It was already reported its capacity to modulate acute and chronic infection [81, 82], inflammatory diseases [82], sepsis [83, 84], neuropathic pain [85], and T-cell activation [86].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [83]
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“The studies discussed in this review strongly demonstrate that pyroptosis and its related pathways play critical roles in sepsis and SAOD, although many questions remain unsolved.”
BackgroundInfluentialA rationale for targeting the P2X7 receptor in Coronavirus disease 19
Di Virgilio, F., Tang, Y., Sarti, A. C., & Rossato, M. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15138 · Cited by 71 · see citing works
Low-Dose Radiation Therapy Promotes Radiation Pneumonitis by Activating NLRP3 Inflammasome
Li, X., Gong, Y., Li, D., Li, X., Ou, Y., Jiang, L., Shu, P., Liu, X., Guo, F., Qin, D., et al. (2020) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2020.02.643 · Cited by 68 · see citing works
Apoptotic cell therapy for cytokine storm associated with acute severe sepsis
Karbian, N., Abutbul, A., el-Amore, R., Eliaz, R., Beeri, R., Reicher, B., & Mevorach, D. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02748-8 · Cited by 63 · see citing works
Signalling by extracellular nucleotides in health and disease
Vultaggio-Poma, V., Falzoni, S., Salvi, G., Giuliani, A. L., & Virgilio, F. D. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2022.119237 · Cited by 59 · see citing works
Guo, Y., Zhang, H., Lv, Z., Du, Y., Li, D., Fang, H., You, J., Yu, L., & Li, R. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01041-3 · Cited by 59 · see citing works
Zou, Z.-J., Wang, Q., Zhou, M.-G., Li, W.-C., Zheng, Y., Li, F.-Y., Zheng, S.-C., & He, Z.-J. (2020) · Journal of Gene Medicine · doi:10.1002/jgm.3261 · Cited by 41 · see citing works
“Extracellular adenosine triphosphate activates P2X7R and then the NLRP3 inflammasome, followed by caspase‐1 activation, which releases mature interleukin (IL)‐1β, thereby promoting inflammation.(13) P2X7R is involved in the process of proinflammatory cytokine production,(12,14) the cell cycle,(15) apoptosis, autophagy…”
BackgroundLiu, Z., Pan, H., Zhang, Y., Zheng, Z., Xiao, W., Hong, X., Chen, F., Peng, X., Pei, Y., Rong, J., et al. (2021) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22885 · Cited by 57 · see citing works
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The Impact of Cytokines on Neutrophils’ Phagocytosis and NET Formation during Sepsis—A Review
Gierlikowska, B., Stachura, A., Gierlikowski, W., & Demkow, U. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23095076 · Cited by 59 · see citing works
Chen, X., Li, H., Wang, K., Liang, X., Wang, W., Hu, X., Huang, Z., & Wang, Y. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01286 · Cited by 56 · see citing works
“Under the action of P2X7R, NLRP3 inflammasome was activated, and then cleaved pro-caspase-1 to form caspase-1, which triggered a series of inflammation (Martinez-Garcia et al., 2019).”
BackgroundMishra, A., Behura, A., Kumar, A., Naik, L., Swain, A., Das, M., Sarangi, S. S., Dokania, P., Dirisala, V. R., Bhutia, S. K., et al. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174235 · Cited by 53 · see citing works
Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells
Wang, L., Ren, C., Yao, R.-Q., Luo, Y., Yin, Y., Wu, Y., Dong, N., Zhu, X.-M., & Yao, Y.-M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03970-z · Cited by 54 · see citing works
“The NLRP3 inflammasome has been confirmed to be activated in monocytes and macrophages under septic conditions [43, 44].”
BackgroundP2X7 receptor in inflammation and pain
Hu, S.-Q., Hu, J., Zou, F.-L., Liu, J., Luo, H., Hu, D.-X., Wu, L., & Zhang, W. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.07.006 · Cited by 50 · see citing works
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“23 Another possibility to explain this absence of responsiveness is that severe or critical COVID-19 patients exhibited a more immature subset of neutrophils associated with an altered response.”
InfluentialDamage associated molecular patterns and neutrophil extracellular traps in acute pancreatitis
Zhou, X., Jin, S., Pan, J., Lin, Q., Yang, S., Ambe, P. C., Basharat, Z., Zimmer, V., Wang, W., & Hong, W. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.927193 · Cited by 51 · see citing works
NLRP3 Inflammasome: A Potential Alternative Therapy Target for Atherosclerosis
Liu, Y., Li, C., Yin, H.-L., Zhang, X., & Li, Y.-L. (2020) · Evidence-Based Complementary and Alternative Medicine · doi:10.1155/2020/1561342 · Cited by 45 · see citing works
“When cells are damaged or necrotic, ATP generated inside the cell is released to outside of the cell to activate the P2X7 ion channel controlled by ATP on the membrane, causing ion transmembrane migration [28].”
BackgroundLi, M., Yang, C., Wang, Y., Song, W., Jia, L., Peng, X., & Zhao, R. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000222 · Cited by 47 · see citing works
“Studies have shown that full-length P2X7R can be released into the circulation, and its blood levels increased in various disease (17, 18).”
BackgroundCD14 release induced by P2X7 receptor restricts inflammation and increases survival during sepsis
Alarcón‐Vila, C., Baroja‐Mazo, A., de Torre‐Minguela, C., Martínez, C. M., Martínez-García, J. J., Martínez‐Banaclocha, H., García-Palenciano, C., & Pelegrı́n, P. (2020) · eLife · doi:10.7554/elife.60849 · Cited by 48 · see citing works
Self-citationHow immune‐cell fate and function are determined by metabolic pathway choice
Kohoutková, M. H., Lázničková, P., & Frič, J. (2020) · BioEssays · doi:10.1002/bies.202000067 · Cited by 47 · see citing works
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Li, W., Cai, Z., Schindler, F., Afjehi-Sadat, L., Montsch, B., Heffeter, P., Heiß, E. H., & Weckwerth, W. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c09132 · Cited by 45 · see citing works
Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury
Strogulski, N. R., Portela, L. V., Polster, B. M., & Loane, D. J. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15959 · Cited by 45 · see citing works
Role of NLRP3 Inflammasomes in Neuroinflammation Diseases
Lin, S., & Mei, X. (2020) · European Neurology · doi:10.1159/000509798 · Cited by 44 · see citing works
Therapeutic implications of inflammasome in inflammatory bowel disease
Khatri, V., & Kalyanasundaram, R. (2021) · The FASEB Journal · doi:10.1096/fj.202002622r · Cited by 47 · see citing works
Arulkumaran, N., Pollen, S., Tidswell, R., Gaupp, C., Peters, V. B. M., Stanzani, G., Snow, T. A. C., Duchen, M. R., & Singer, M. (2021) · British Journal of Anaesthesia · doi:10.1016/j.bja.2021.05.036 · Cited by 42 · see citing works
Canonical and non-canonical functions of NLRP3
Accogli, T., Hibos, C., & Végran, F. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.01.001 · Cited by 43 · see citing works
Liang, S., Zhou, J., Cao, C., Liu, Y., Ming, S., Liu, X., Shang, Y., Lao, J., Qin, P., Yang, J., et al. (2024) · Cellular and Molecular Immunology · doi:10.1038/s41423-024-01170-w · Cited by 42 · see citing works
“All patients were selected based on clinical diagnosis and laboratory information.”
Xie, S., Qi, X., Wu, Q., Li, W., Zhang, M., Yun, X., Shi, W., Chen, S., Zeng, X., Wang, S., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.02.034 · Cited by 42 · see citing works
Joshi, S., Kundu, S., Priya, V. V., Kulhari, U., Mugale, M. N., & Sahu, B. D. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121743 · Cited by 41 · see citing works
Mokmeli, S., & Vetrici, M. A. (2020) · Canadian Journal of Respiratory Therapy · doi:10.29390/cjrt-2020-015 · Cited by 41 · see citing works
“Extracellular ATP plays a central role in apoptotic cell death [27], the induction of inflammation [28], and mitochondrial failure in monocytes [29].”
BackgroundLipid oxidation dysregulation: an emerging player in the pathophysiology of sepsis
Muniz‐Santos, R., Costa, G. L. A., de Almeida, M. A. P., Moraes-de-Souza, I., Brito, M. A. D. S. M., Silva, A. R., & Gonçalves-de-Albuquerque, C. F. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1224335 · Cited by 41 · see citing works
Molina‐López, C., Hurtado‐Navarro, L., García, C. J., Angosto-Bazarra, D., Vallejo, F., Tapia‐Abellán, A., Marques-Soares, J. R., Vargas, C., Buján-Rivas, S., Tomás-Barberán, F. A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-44990-0 · Cited by 40 · see citing works
Self-citationGut Enterobacteriaceae and uraemic toxins - Perpetrators for ageing
Boopathi, S., Kumar, R. M. S., Priya, P. S., Haridevamuthu, B., Nayak, S. P. R. R., Chulenbayeva, L., Kushugulova, A. R., & Arockiaraj, J. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112088 · Cited by 40 · see citing works
“In addition to curli fibres, endotoxin from Enterobacteriaceae can stimulate the activation of NLRP3 inflammasome (Martínez-García et al., 2019).”
BackgroundPurinergic signalling in host innate immune defence against intracellular pathogens
Coutinho‐Silva, R., & Savio, L. E. B. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114405 · Cited by 39 · see citing works
Saber, S., Yahya, G., Gobba, N. A., Sharaf, H., Alshaman, R., Alattar, A., Amin, N. A., El-Shedody, R., Aboutouk, F. H., El-Galeel, Y. A., et al. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s315938 · Cited by 38 · see citing works
The prognostic impact of SIGLEC5-induced impairment of CD8+ T cell activation in sepsis
Lozano‐Rodríguez, R., Ortiz, J. A., Montalbán-Hernández, K. M., Ruiz‐Rodríguez, J. C., Ferrer, R., Martín‐Quirós, A., Maroun‐Eid, C., González‐López, J. J., Fàbrega, A., Terrón‐Arcos, V., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104841 · Cited by 44 · see citing works
Self-citationGarcía-Villalba, J., Hurtado‐Navarro, L., Peñín‐Franch, A., Molina‐López, C., Martínez-Alarcón, L., Angosto-Bazarra, D., Baroja‐Mazo, A., & Pelegrı́n, P. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.894470 · Cited by 37 · see citing works
“In diseases satisfactorily treated with anti-IL-1 therapy, such as sepsis or autoinflammatory syndromes, the blood concentrations of IL-1b are very low and usually not detected (33, 43).”
BackgroundSelf-citationGalvanic current activates the NLRP3 inflammasome to promote Type I collagen production in tendon
Peñín‐Franch, A., García-Vidal, J. A., Martínez, C. M., Escolar‐Reina, P., Martínez-Ojeda, R. M., Gómez, A. I., Bueno, J. M., Minaya‐Muñoz, F., Valera‐Garrido, F., Medina‐Mirapeix, F., et al. (2022) · eLife · doi:10.7554/elife.73675 · Cited by 36 · see citing works
Self-citationMacrophage polarization in sepsis: Emerging role and clinical application prospect
Hou, F., Mi, J. H., Wang, Q., Tao, Y. L., bin Guo, S., Ran, G. H., & Wang, J. C. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113715 · Cited by 36 · see citing works
HGF alleviates septic endothelial injury by inhibiting pyroptosis via the mTOR signalling pathway
Peng, F., Chang, W., Sun, Q., Xu, X., Xie, J., Qiu, H., & Yang, Y. (2020) · Respiratory Research · doi:10.1186/s12931-020-01480-3 · Cited by 36 · see citing works
Circulating P2X7 Receptor Signaling Components as Diagnostic Biomarkers for Temporal Lobe Epilepsy
Conte, G., Menéndez‐Méndez, A., Bauer, S., Naggar, H. E., Alves, M., Nicke, A., Delanty, N., Rosenow, F., Henshall, D. C., & Engel, T. (2021) · Cells · doi:10.3390/cells10092444 · Cited by 36 · see citing works
“While promising, we acknowledge, however, that changes in P2X7R protein levels in plasma are not unique to seizures and epilepsy and, as mentioned above, have been previously reported for different pathological conditions [30,31,53,60].”
BackgroundResultInfluentialTo Inhibit or Enhance? Is There a Benefit to Positive Allosteric Modulation of P2X Receptors?
Stokes, L., Bidula, S., Bibic, L., & Allum, E. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00627 · Cited by 34 · see citing works
Role of CD39 in COVID-19 Severity: Dysregulation of Purinergic Signaling and Thromboinflammation
Díaz‐García, E., García-Tovar, S., Alfaro, E., Zamarrón, E., Mangas-Moro, A., Galera, R., Ruiz-Hernández, J. J., Solé‐Violán, J., Rodríguez‐Gallego, C., Rym, A. M. V. D., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.847894 · Cited by 35 · see citing works
“eATP constitutes an important alarm for the immune system (36) as it is recognized by P2X7R, the most relevant purinergic receptor involved in inflammatory processes (37), such as sepsis (38).”
BackgroundEmerging Role of NLRP3 Inflammasome and Pyroptosis in Liver Transplantation
Lucas‐Ruiz, F., Peñín‐Franch, A., Pons, J. A., Ramírez, P., Pelegrı́n, P., Cuevas, S., & Baroja‐Mazo, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214396 · Cited by 35 · see citing works
Self-citationCui, J., He, Y., Zhu, F., Gong, W., Zuo, R., Wang, Y., Luo, Y., Chen, L., Wang, C., Huo, G., et al. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.82980 · Cited by 34 · see citing works
“HMGB1 is a main proinflammatory factor released by pyroptotic cells as a result of plasma membrane rupture and leakage[41].”
BackgroundGAS6 attenuates sepsis-induced cardiac dysfunction through NLRP3 inflammasome-dependent mechanism
Ji, T., Liu, Q., Yu, L., Lei, W., Lu, C., Chen, J., Xie, X., Zhang, Z., Liang, Z., Deng, C., et al. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.11.007 · Cited by 34 · see citing works
The roles of NLRP3 inflammasome in bacterial infection
Zhong, Y., Lu, Y., Yang, X., Tang, Y., Zhao, K., Yuan, C., & Zhong, X. (2020) · Molecular Immunology · doi:10.1016/j.molimm.2020.03.020 · Cited by 34 · see citing works
Chen, P., An, Q., Huang, Y., Zhang, M., & Mao, S. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174438 · Cited by 33 · see citing works
Neutrophils Facilitate Prolonged Inflammasome Response in the DAMP-Rich Inflammatory Milieu
Son, S., Yoon, S.-H., Chae, B. J., Hwang, I., Shim, D.-W., Choe, Y. H., Hyun, Y., & Yu, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.746032 · Cited by 33 · see citing works
Yang, S., Hua, K., Chu, L. J., Hwu, Y., Yang, S., Wu, C.-Y., Lin, T.-J., Weng, J.-C., Zhao, H., Hsu, W., et al. (2020) · Kidney International · doi:10.1016/j.kint.2020.02.033 · Cited by 30 · see citing works
P2RX7 at the Host-Pathogen Interface of Infectious Diseases
Soare, A., Freeman, T. L., Min, A. K., Malik, H. S., Osota, E. O., & Swartz, T. H. (2021) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00055-20 · Cited by 25 · see citing works
The double sides of NLRP3 inflammasome activation in sepsis
Vigneron, C., Py, B. F., Monneret, G., & Venet, F. (2023) · Clinical Science · doi:10.1042/cs20220556 · Cited by 33 · see citing works
Ghait, M., Duduskar, S. N., Rooney, M. D., Häfner, N., Reng, L., Göhrig, B., Reuken, P. A., Bloos, F., Bauer, M. W., Sponholz, C., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1239474 · Cited by 29 · see citing works
Zhu, J., Zhang, M., Han, T.-L., Wu, H., Xiao, Z., Lin, S., Wang, C., & Xu, F. (2019) · BioMed Research International · doi:10.1155/2019/2612849 · Cited by 29 · see citing works
“-e expression level if HIF-1 can be induced in response to reduced oxygen availability and other stimulants (such as nitric oxide (NO) or various growth factors) in metabolic processes [14].”
BackgroundP2RX7 Enhances Tumor Control by CD8+ T Cells in Adoptive Cell Therapy
Wanhainen, K. M., Peng, C., Zhou, M. H., Macedo, B. D. G., O’Flanagan, S. D., Yang, T., Kelekar, A., Burbach, B. J., da Silva, H. B., & Jameson, S. C. (2022) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-21-0691 · Cited by 29 · see citing works
Gonçalves-Pereira, J., Fernandes, J., Duarte, A. R., & Fernandes, S. M. (2022) · Antibiotics · doi:10.3390/antibiotics11121839 · Cited by 30 · see citing works
Alves, V. S., da Silva, J. P., Rodrigues, F. C., Araújo, S. M. B., Gouvêa, A. L., Leite-Aguiar, R., Santos, S. A. C. S., da Silva, M. S. P., Ferreira, F. S., Marques, E. P., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1179723 · Cited by 29 · see citing works
“Interestingly, P2X7 receptor expression increases on the surface of monocytes from septic patients (Martínez-García et al., 2019), and P2X7 receptor gain-offunction single nucleotide polymorphisms increased susceptibility to developing severe sepsis (Geistlinger et al.”
BackgroundThe P2X7 Receptor as a Mechanistic Biomarker for Epilepsy
Engel, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065410 · Cited by 28 · see citing works
Togre, N. S., Mekala, N., Bhoj, P., Mogadala, N., Winfield, M., Trivedi, J., Grove, D., Kotnala, S., Rom, S., Sriram, U., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03230-4 · Cited by 23 · see citing works
CMPK2 accelerates liver ischemia/reperfusion injury via the NLRP3 signaling pathway
Luo, Y., Zheng, D., Mou, T., Pu, J., Huang, Z., Chen, W., Zhang, Y., & Wu, Z. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10793 · Cited by 27 · see citing works
“Uncontrollable NLRP3 inflammasome is associated with several diseases, such as atherosclerosis (9), sepsis (10), Crohn's disease (11), acute myocardial infarction (12) and cancer (13).”
BackgroundThe role of P2X7 receptor in infection and metabolism: Based on inflammation and immunity
Cai, X. T., Yao, Y., Teng, F., Li, Y., Wu, L., Yan, W., & Lin, N. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108297 · Cited by 27 · see citing works
Reprogramming Macrophage Metabolism and its Effect on NLRP3 Inflammasome Activation in Sepsis
Luo, R., Li, X., & Wang, D. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.917818 · Cited by 27 · see citing works
“Inflammasomes are a class of pattern-recognition receptors (PPRs) located in the cytoplasm and were first detected in 2002 (Martinon et al., 2002).”
BackgroundAnimal Models for the Investigation of P2X7 Receptors
Sluyter, R., Adriouch, S., Fuller, S. J., Nicke, A., Sophocleous, R. A., & Watson, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098225 · Cited by 26 · see citing works
Self-citationRepositioning linifanib as a potent anti-necroptosis agent for sepsis
Yu, L., Yang, K., He, X., Li, M., Gao, L., & Zha, Y. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01351-y · Cited by 26 · see citing works
Hu, Y., Li, Q., Pan, Y., & Li, X. (2019) · Molecules · doi:10.3390/molecules24234416 · Cited by 25 · see citing works
“As a component of inn te immunity [21], the NLRP3 inflam asome plays an important role in many inflammatory diseases [22,23].”
BackgroundZhang, Y., Zhang, J., Ren, Y., Li, T., Bi, J., Du, Z., & Wu, R. (2020) · Shock · doi:10.1097/shk.0000000000001624 · Cited by 25 · see citing works
“A recent study revealed that most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered (32).”
BackgroundZalpoor, H., Akbari, A., Nabi‐Afjadi, M., Forghaniesfidvajani, R., Tavakol, C., Barzegar, Z., Iravanpour, F., Hosseini, M., Mousavi, S. R., & Farrokhi, M. R. (2022) · Human Cell · doi:10.1007/s13577-022-00747-9 · Cited by 25 · see citing works
Adu‐Amankwaah, J., Adekunle, A. O., Tang, Z., Bushi, A., Tan, R., Fu, L., Gong, Z., Ma, Z., Mprah, R., Noah, M. L. N., et al. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155934 · Cited by 25 · see citing works
Immunotherapy in the context of sepsis-induced immunological dysregulation
Wu, Y.-Q., Wang, L., Li, Y., Cao, Y., Wang, M., Deng, Z.-H., & Kang, H.-J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1391395 · Cited by 27 · see citing works
Detection of In Vivo Inflammasome Activation for Predicting Sepsis Mortality
Cui, J. Z., Oehrl, S., Ahmad, F., Brenner, T., Uhle, F., Nußhag, C., Rupp, C., Funck, F., Meisel, S., Weigand, M. A., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.613745 · Cited by 24 · see citing works
“Inflammasome research and monocyte function are of particular interest in sepsis (18, 20, 21).”
BackgroundInfluentialMekala, N. K., Gheewala, N., Rom, S., Sriram, U., & Persidsky, Y. (2022) · Antioxidants · doi:10.3390/antiox11071328 · Cited by 24 · see citing works
Cai, S., Fan, X., Wu, J., Wang, Y., Hu, X., Pei, S., Zheng, Y., Chen, J., Huang, Y., Li, N., et al. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-01037-8 · Cited by 25 · see citing works
“For example, HIF-1α is involved in metabolic reprogramming to glycolysis and in the production of proinflammatory cytokines and chemokines during sepsis [55, 56].”
BackgroundZhang, M., Zheng, R., Liu, W., Hou, J.-L., Yang, Y., & Shang, H. (2023) · Journal of Chinese Integrative Medicine · doi:10.1016/j.joim.2023.08.004 · Cited by 24 · see citing works
Signaling Through Purinergic Receptor P2Y2 Enhances Macrophage IL-1β Production
de la Rosa, G., Gómez, A. I., Baños, M. C., & Pelegrı́n, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134686 · Cited by 24 · see citing works
“On the contrary, when extracellular ATP concentration rises to the mM range and P2X7R activates before macrophage priming with endotoxin, we recently found that the activity of NLRP3 inflammasome is reduced [7].”
BackgroundKorhonen, E., Hytti, M., Piippo, N., Kaarniranta, K., & Kauppinen, A. (2021) · Experimental Eye Research · doi:10.1016/j.exer.2021.108687 · Cited by 23 · see citing works
Js, K., Mun, S., Cho, E., Kim, D.-G., Son, W., Jeon, H.-I., Kim, H. K., Jang, K., & Yang, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228437 · Cited by 22 · see citing works
“However, NLRP3 activation was shown to be impaired by the P2 × 7 receptor in monocytes from a patient with an immunocompromised status caused by mitochondrial dysfunction and the inhibition of NLRP3 activation by HIF-1α [50].”
BackgroundLu, F., Chen, H., Hong, Y., Lin, Y., Liu, L., Wei, N., Wu, Q., Liao, S., Yang, S., He, J., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-92547-8 · Cited by 21 · see citing works
Multiple Targets for Oxysterols in Their Regulation of the Immune System
Reinmuth, L., Hsiao, C., Hamann, J., ROSENKILDE, M. M., & Mackrill, J. J. (2021) · Cells · doi:10.3390/cells10082078 · Cited by 20 · see citing works
“Extracellular ATP promotes the activation of the NLRP3-inflammosome in monocytes and this process is impaired during sepsis [148].”
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Interplay between inflammasomes and PD-1/PD-L1 and their implications in cancer immunotherapy
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P2X7 receptor antagonist A-438079 alleviates oxidative stress of lung in LPS-induced septic rats
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“P2X7Rs are activated in the monocytes of patients with sepsis [18] and LPS administration increases P2X7R immuno-expression in lung parenchyma while macrophages are not activated in P2X7R knockout mice [19].”
- Authors
- Martínez-García, J. J., Martínez-Banaclocha, H., Angosto-Bazarra, D., de Torre-Minguela, C., Baroja-Mazo, A., Alarcón-Vila, C., Martínez-Alarcón, L., Amores-Iniesta, J., Martín-Sánchez, F., Ercole, G. A., Martínez, C. M., González-Lisorge, A., Fernández-Pacheco, J., Martínez-Gil, P., Adriouch, S., Koch-Nolte, F., Luján, J., Acosta-Villegas, F., Parrilla, P., García-Palenciano, C., & Pelegrin, P.
- Affiliations
- Instituto Murciano de Investigación Biosanitaria (ES)
- Hospital Universitario Virgen de la Arrixaca (ES)
- Inserm (FR)
- ORCID
- Venue
- Nature Communications
- Published
- 2019-06-20
- Volume
- 10
- Issue
- 1
- Pages
- 2711-2711
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6586640
- OpenAlex
- W2952125019
- Cited by
- 233
- References
- 63
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 44 · 2023: 48 · 2022: 39 · 2021: 34 · 2020: 33 · 2019: 3
- FWCI
- 9.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Hispana (publishedVersion, cc-by)
- HAL (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Institute for Research in Biomedicine
- Ablynx
- European Cooperation in Science and Technology (BM-1406)
- Ministerio de Economía y Competitividad (FJCI-2014-22041, PI13/00174, CD13/00059)
- Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España (SAF2017‐88276‐R)
- European Regional Development Fund (PI13/00174)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- P2X7 receptor, NLRP3 inflammasome, mitochondrial dysfunction, monocytes, sepsis, HIF-1α, purinergic signaling, immunosuppression, sepsis mortality, abdominal sepsis, mouse sepsis model
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Adult, Aged, Aged, 80 and over, Animals, Disease Models, Animal, Female, Follow-Up Studies, Humans, Macrophages, Male, Middle Aged, Mitochondria, Monocytes, Up-Regulation, Sepsis, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Receptors, Purinergic P2X7, Inflammasomes, Mitochondrial Dynamics
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