Cited by 838Inflammasome and immune disordersImmune Response and InflammationAutoimmune and Inflammatory Disorders Research

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NLRP3 inflammasome and its inhibitors: a review

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Shao, Bo-Zong, Xu, Zhe-Qi, Han, Bin-Ze, Su, Ding-Feng, Liu, Chong·2015·Frontiers in Pharmacology

DOI 10.3389/fphar.2015.00262PMC PMC4633676

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Abstract

Inflammasomes are newly recognized, vital players in innate immunity. The best characterized is the NLRP3 inflammasome, so-called because the NLRP3 protein in the complex belongs to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs) and is also known as "pyrin domain-containing protein 3". The NLRP3 inflammasome is associated with onset and progression of various diseases, including metabolic disorders, multiple sclerosis, inflammatory bowel disease, cryopyrin-associated periodic fever syndrome, as well as other auto-immune and auto-inflammatory diseases. Several NLRP3 inflammasome inhibitors have been described, some of which show promise in the clinic. The present review will describe the structure and mechanisms of activation of the NLRP3 inflammasome, its association with various auto-immune and auto-inflammatory diseases, and the state of research into NLRP3 inflammasome inhibitors.

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Background
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BackgroundMethod
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Background
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Background
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Background
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Background
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Background
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Background
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Background
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Background
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Background
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Self-citation
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Background
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BackgroundInfluential
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Background
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Background
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The P2X7 Receptor in Osteoarthritis
Li, Z., Huang, Z., & Bai, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.628330 · Cited by 42
“NLRP3 activates caspase-1, promoting the secretion of IL-1β and IL18 to exacerbate inflammation (Shao et al., 2015), resulting in rapid cell death (Latz et al., 2013).”
Background
Caspase‐1‐Inhibitor AC‐YVAD‐CMK Inhibits Pyroptosis and Ameliorates Acute Kidney Injury in a Model of Sepsis
Yang, M., Fang, J., Zhang, N.-S., Qin, L.-J., Zhuang, Y.-Y., Wang, W., Zhu, H., Zhang, Y., Xia, P., & Zhang, Y. (2021) · BioMed Research International · doi:10.1155/2021/6636621 · Cited by 42
“As the center of inflammatory response, inflammatory bodies are closely related to various diseases, including immune inflammatory diseases, metabolic diseases, and nervous system diseases, especially playing a key role in infectious diseases [4].”
Background
NLRP3 and Infections: β-Amyloid in Inflammasome beyond Neurodegeneration
Sita, G., Graziosi, A., Hrelia, P., & Morroni, F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136984 · Cited by 43
Lysophosphatidylcholine induces apoptosis and inflammatory damage in brain microvascular endothelial cells via GPR4-mediated NLRP3 inflammasome activation
Liu, T., Wang, X., Guo, F., Sun, X., Yuan, K., Wang, Q., & Lan, C. (2021) · Toxicology in Vitro · doi:10.1016/j.tiv.2021.105227 · Cited by 42
The role of NLRP3 inflammasome in type 2 inflammation related diseases
Xu, S., Wang, D., Tan, L., & Lu, J. (2024) · Autoimmunity · doi:10.1080/08916934.2024.2310269 · Cited by 43
“This results in the up-regulation of various inflammasome-associated components (pro IL-1β, and pro IL-18), including NLRP3 [11,13–18].”
Network pharmacology analysis and animal experiment validation of neuroinflammation inhibition by total ginsenoside in treating CSM
Li, Z.-Y., Dai, Y.-X., Wu, Z., Gan, L., Pu, P., Hu, C.-W., Zhou, L., Zhu, K., Shu, B., Wang, Y., et al. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.155073 · Cited by 41
Mast cell inflammasome activity in the meninges regulates EAE disease severity
Russi, A. E., Caulfield, M. E., & Brown, M. A. (2016) · Clinical Immunology · doi:10.1016/j.clim.2016.04.009 · Cited by 41
Connexins-Based Hemichannels/Channels and Their Relationship with Inflammation, Seizures and Epilepsy
Medina‐Ceja, L., Salazar‐Sánchez, J. C., Ortega‐Ibarra, J., & Morales‐Villagrán, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20235976 · Cited by 41
Inflammation and Severe Cerebral Venous Thrombosis
Hu, S., Lee, H., Zhao, H., Ding, Y., & Duan, J. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.873802 · Cited by 40
Role of NLRP3 Inflammasome in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis with Nasal Polyps
Lin, H. P., Li, Z., Lin, D., Zheng, C., & Zhang, W. (2016) · Inflammation · doi:10.1007/s10753-016-0442-z · Cited by 40
“NLRP3, also known as cryopyrin, a member of the NLR family, can be activated by pathogens, sterile tissue damage, or metabolic stress and plays a pivotal role in the process of inflammatory reactions [8, 9].”
Background
RETRACTED ARTICLE: Activation of the NLRP3 Inflammasome Is Associated with Valosin-Containing Protein Myopathy
Nalbandian, A., Khan, A. A., Srivastava, R., Llewellyn, K. J., Tan, B., Shukr, N., Fazli, Y., Kimonis, V. E., & BenMohamed, L. (2016) · Inflammation · doi:10.1007/s10753-016-0449-5 · Cited by 42
“Several NLRP3 inflammasome inhibitors have been previously described; some of which show promise in the clinic (as reviewed in [56]).”
Retracted
Innate immunity and clinical hypertension
Beusecum, J. P. V., Moreno, H., & Harrison, D. G. (2021) · Journal of Human Hypertension · doi:10.1038/s41371-021-00627-z · Cited by 41
“Factors in the hypertensive milieu, including the vasoactive molecules ang II, aldosterone, and endothelin-1 are able to activate the NLRP3 (nucleotide oligomerization domain-like receptor family pyrin domain containing 3) inflammasome [48].”
Background
Anti-Inflammation and Anti-Pyroptosis Activities of Mangiferin via Suppressing NF-κB/NLRP3/GSDMD Signaling Cascades
Feng, M. H., Wei, S., Zhang, S., & Yang, Y. N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231710124 · Cited by 43
Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation
Yan, J., Ding, D., Feng, G., Yang, Y., Zhou, Y., Ma, L., Guo, H., Lü, Z., & Jin, Q. (2022) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2022.11146 · Cited by 39
“The typical activation pathway of pyroptosis is mediated by the NOD‐like receptor protein 3 (NLRP3) inflammasome, which mainly includes NLRP3, apoptosis‐associated speck‐like protein containing CARD (ASC) and pro‐caspase‐1 (10).”
Background
GSDMD contributes to myocardial reperfusion injury by regulating pyroptosis
Ye, X., Zhang, P., Zhang, Y., Luan, J., Xu, C., Wu, Z., Ju, D., & Hu, W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.893914 · Cited by 39
NLRP3 Inflammasome Mediates Dormant Neutrophil Recruitment following Sterile Lung Injury and Protects against Subsequent Bacterial Pneumonia in Mice
Tian, X., Sun, H., Casbon, A.-J., Lim, E., Francis, K. P., Hellman, J., & Prakash, A. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01337 · Cited by 38
Isofraxidin Alleviates Myocardial Infarction Through NLRP3 Inflammasome Inhibition
Chen, G., Song, X., Lin, D., & Xu, P. (2020) · Inflammation · doi:10.1007/s10753-019-01158-z · Cited by 39
Novel insights into antidepressant mechanism of Kai Xin San formula: Inhibiting NLRP3 inflammasome activation by promoting autophagy
Yu, S., Liu, S., Wang, N., Yu, D., Qin, M., Wu, J., & Guan, Q. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153792 · Cited by 42
Contradictory Effects of NLRP3 Inflammasome Regulatory Mechanisms in Colitis
Wagatsuma, K., & Nakase, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218145 · Cited by 38
Diet-induced obesity impairs spermatogenesis: the critical role of NLRP3 in Sertoli cells
Yang, M., Yin, T., Zhang, Y., Yang, J., & Wu, Y. (2022) · Inflammation and Regeneration · doi:10.1186/s41232-022-00203-z · Cited by 38
“the most studied inflammasome and comprises NLRP3, apoptosis-associated speck-like protein (ASC), and procaspase-1 [19].”
Background
Essential Minerals and Metabolic Adaptation of Immune Cells
Alghamdi, M. A., Gutierrez, J., & Komarnytsky, S. (2022) · Nutrients · doi:10.3390/nu15010123 · Cited by 44
PCSK9 Inhibition Reduces Depressive like Behavior in CUMS-Exposed Rats: Highlights on HMGB1/RAGE/TLR4 Pathway, NLRP3 Inflammasome Complex and IDO-1
Hendawy, N., Salaheldin, T. H., & Abuelezz, S. A. (2023) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-023-10060-3 · Cited by 38
Anti-Inflammatory Effects of Minor Cannabinoids CBC, THCV, and CBN in Human Macrophages
Gojani, E. G., Wang, B., Li, D., Kovalchuk, O., & Kovalchuk, I. (2023) · Molecules · doi:10.3390/molecules28186487 · Cited by 42
Multifactorial Activation of NLRP3 Inflammasome: Relevance for a Precision Approach to Atherosclerotic Cardiovascular Risk and Disease
Baragetti, A., Catapano, A. L., & Magni, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124459 · Cited by 39
TRIM31 inhibits NLRP3 inflammasome and pyroptosis of retinal pigment epithelial cells through ubiquitination of NLRP3
Huang, P., Liu, W., Chen, J., Hu, Y., Wang, Y., Sun, J., & Feng, J. (2020) · Cell Biology International · doi:10.1002/cbin.11429 · Cited by 38
Bone marrow stromal cells attenuate LPS-induced mouse acute liver injury via the prostaglandin E 2-dependent repression of the NLRP3 inflammasome in Kupffer cells
Miao, C., Jiang, X.-W., He, K., Li, P., Liu, Z., Cao, D., Ou, Z.-B., Gong, J., Liu, C., & Cheng, Y. (2016) · Immunology Letters · doi:10.1016/j.imlet.2016.09.009 · Cited by 37
Self-citation
Cordycepin inhibits LPS-induced inflammatory responses by modulating NOD-Like Receptor Protein 3 inflammasome activation
Yang, J., Li, Y., Hylemon, P. B., Zhang, L., & Zhou, H. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.09.103 · Cited by 37
Involvement of Innate Immune System in Late Stages of Inherited Photoreceptor Degeneration
Sudharsan, R., Beiting, D. P., Aguirre, G. D., & Beltran, W. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-18236-7 · Cited by 37
Development of covalent NLRP3 inflammasome inhibitors: Chemistry and biological activity
Bertinaria, M., Gastaldi, S., Marini, E., & Giorgis, M. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.11.013 · Cited by 38
“While specifically designed NLRP3 inhibitors have yet to reach the drug market, a number of small molecule inhibitors of the NLRP3 inflammasome have been developed [46,47].”
Background
Deoxynivalenol aggravates the immunosuppression in piglets and PAMs under the condition of PEDV infection through inhibiting TLR4/NLRP3 signaling pathway
Liu, D., Wang, Q., He, W., Ge, L., & Huang, K. (2022) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2022.113209 · Cited by 36
Curcumin Alleviates Aflatoxin B1-Induced Liver Pyroptosis and Fibrosis by Regulating the JAK2/NLRP3 Signaling Pathway in Ducks
Cui, Y., Wang, Q., Zhang, X., Yang, X., Shi, Y., Li, Y., & Song, M. (2023) · Foods · doi:10.3390/foods12051006 · Cited by 36
Salvianolic Acid A Ameliorates Early-Stage Atherosclerosis Development by Inhibiting NLRP3 Inflammasome Activation in Zucker Diabetic Fatty Rats
Ma, Q., Yang, Q., Chen, J., Yu, C., Zhang, L., Zhou, W., & Chen, M. (2020) · Molecules · doi:10.3390/molecules25051089 · Cited by 36
The P2X7 Receptor and NLRP3 Axis in Non-Alcoholic Fatty Liver Disease: A Brief Review
Rossato, M., Vincenzo, A. D., Pagano, C., Hadi, H. E., & Vettor, R. (2020) · Cells · doi:10.3390/cells9041047 · Cited by 36
Trueperella pyogenes pyolysin inhibits lipopolysaccharide-induced inflammatory response in endometrium stromal cells via autophagy- and ATF6-dependent mechanism
Qi, M., Liu, J., Jiang, Q., Niu, H., Wang, X., Zhou, D., Lin, P., Chen, H., Wang, A., & Jin, Y. (2021) · Brazilian Journal of Microbiology · doi:10.1007/s42770-021-00422-5 · Cited by 35
Inflammation, Apoptosis, and Fibrosis in Diabetic Nephropathy: Molecular Crosstalk in Proximal Tubular Epithelial Cells and Therapeutic Implications
Liu, X., Zhang, C., Fu, Y., Xie, L., Kong, Y., & Yang, X. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47110885 · Cited by 39
Hypothermic oxygenated perfusion (HOPE) attenuates ischemia/reperfusion injury in the liver through inhibition of the TXNIP/NLRP3 inflammasome pathway in a rat model of donation after cardiac death
He, W., Ye, S., Zeng, C., Xue, S., Hu, X., Zhang, X., Gao, S., Xiong, Y., He, X., Vivalda, S., et al. (2018) · The FASEB Journal · doi:10.1096/fj.201800028rr · Cited by 35
“NOD-like receptor protein 3 (NLRP3), which belongs to the Nod-like receptor family, can recognize DAMPs and subsequently activates the NLRP3 inflammasome that plays a role in sterile inflammatory response (15, 16).”
Background
Inhibitory Role of Berberine, an Isoquinoline Alkaloid, on NLRP3 Inflammasome Activation for the Treatment of Inflammatory Diseases
Sarbadhikary, P., George, B. P. A., & Abrahamse, H. (2021) · Molecules · doi:10.3390/molecules26206238 · Cited by 38
Oridonin Protects against Myocardial Ischemia–Reperfusion Injury by Inhibiting GSDMD-Mediated Pyroptosis
Lin, J., Lai, X., Fan, X., Ye, B., Zhong, L., Zhang, Y., Shao, R., Shi, S., Huang, W., Su, L., et al. (2022) · Genes · doi:10.3390/genes13112133 · Cited by 37
Characterization of NLRP3 Inflammasome Activation in the Onset of Diabetic Retinopathy
Kuo, C. Y. J., Maran, J. J., Jamieson, E. G., Rupenthal, I. D., Murphy, R., & Mugisho, O. O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214471 · Cited by 35
Mechanistic and therapeutic insights into the function of NLRP3 inflammasome in sterile arthritis
Xiao, Y., & Zhang, L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1273174 · Cited by 36

Authors: Shao, B.-Z., Xu, Z.-Q., Han, B.-Z., Su, D.-F., & Liu, C.
Affiliations: Second Military Medical University (CN)
Corresponding author: Liu, Chong
ORCID: Shao, Bo-Zong
Su, Ding-Feng
Liu, Chong
Venue: Frontiers in Pharmacology
Publisher: Frontiers Media SA
Published: 2015-11-05
Volume: 6
Pages: 262-262
ISSN: 1663-9812 (ISSN-L)
DOI: 10.3389/fphar.2015.00262
PMC: PMC4633676
OpenAlex: W2137444266
Cited by: 836
References: 115
Citations by year: 2026: 42 · 2025: 62 · 2024: 102 · 2023: 107 · 2022: 114 · 2021: 105 · 2020: 91 · 2019: 68 · 2018: 61 · 2017: 57 · 2016: 24 · 2015: 2
FWCI: 4.60
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Pharmacology (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)
Frontiers in Pharmacology (cc-by)
Funders: Natural Science Foundation of Shanghai (13ZR1448400)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Keywords: NLRP3 inflammasome, inflammasome inhibitors, innate immunity, autoinflammatory disease, autoimmune disease, metabolic disorders, multiple sclerosis, inflammatory bowel disease

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NLRP3 inflammasome and its inhibitors: a review

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