- •Macrophage pyroptosis was increased in SSc patients and BLM-induced SSc mouse model.
- •Inhibition of pyroptosis reduced inflammation and fibrosis of SSc mouse model.
- •Inhibiting NLRP3/GSDMD-mediated macrophage pyroptosis inactivates fibroblasts.
Abbreviations:ASC (Apoptosis-associated speck-like protein containing a caspase recruitment domain), α-SMA (α-Smooth muscle actin), BLM (Bleomycin), BMDMs (Mouse bone marrow-derived macrophages), CASP1 (Caspase-1), DAPI (4′,6-diamidino-2-phenylindole), ELISA (Enzyme-linked immunosorbent assay), FBS (Fetal bovine serum), GSDMD (Gasdermin D), GSDMD-N (GSDMD N-terminal), HCs (Healthy controls), H&E (Hematoxylin and eosin), IL-1β (Interleukin-1β), IL-18 (Interleukin-18), LPS (Lipopolysaccharide), LDH (Lactate dehydrogenase), M-CSF (Macrophage colony-stimulating factor), NLRs (Nod-like receptors), NLRP3 (NLRs family pyrin domain containing 3), NSA (Necrosulfonamide), PMA (Phorbol 12-myristate 13-acetate), PI (Propidium iodide), SiO2 (Silicon dioxide), SSc (Systemic sclerosis), THP-1 (Human acute monocytic leukemia cell line)
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
- Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis.J. Clin. Invest. 2020; 130: 2451-2464
- Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile.Ann. Rheum. Dis. 2020; 79: 379-386
- BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance.Sci. Adv. 2018; 4: eaas9944
- Innate immunity in systemic sclerosis fibrosis: recent advances.Front Immunol. 2018; 9: 1702
- The roles of IL-1 family cytokines in the pathogenesis of systemic sclerosis.Front Immunol. 2019; 10: 2025
- Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death.Nature. 2015; 526: 660-665
- Inflammasomes: mechanism of assembly, regulation and signalling.Nat. Rev. Immunol. 2016; 16: 407-420
- Expression of NLRP3 inflammasome, cytokines and vascular mediators in the skin of systemic sclerosis patients.Isr. Med Assoc. J. 2015; 17: 5-10
- Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes.Cell. 2014; 156: 1193-1206
- Activation and regulation of the inflammasomes.Nat. Rev. Immunol. 2013; 13: 397-411
- The neglected association of crystalline silica exposure and systemic sclerosis.Rheumatology. 2020; 59: 3587-3588
- Occupational silica exposure in an Australian systemic sclerosis cohort.Rheumatology. 2020; 59: 3900-3905
- Association of interleukin 1 family with systemic sclerosis.Inflammation. 2014; 37: 1213-1220
- Role of pyruvate kinase M2 in oxidized LDL-induced macrophage foam cell formation and inflammation.J. Lipid Res. 2020; 61: 351-364
- Characterization of the phenotype of high collagen-producing fibroblast clones in systemic sclerosis, using a new modified limiting-dilution method.Clin. Exp. Dermatol. 2012; 37: 395-403
- Autophagy mediates 2-methoxyestradiol-inhibited scleroderma collagen synthesis and endothelial-to-mesenchymal transition induced by hypoxia.Rheumatology. 2019; 58: 1966-1975
- Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis.J. Hepatol. 2021; 74: 156-167
- Lycorine ameliorates bleomycin-induced pulmonary fibrosis via inhibiting NLRP3 inflammasome activation and pyroptosis.Pharm. Res. 2020; 158104884
- An NLRP3-specific inflammasome inhibitor attenuates crystal-induced kidney fibrosis in mice.Kidney Int. 2016; 90: 525-539
- Killer jeans and silicosis.Am. J. Respir. Crit. Care Med. 2011; 184: 1322-1324
- SR-B1 is a silica receptor that mediates canonical inflammasome activation.Cell Rep. 2017; 18: 1298-1311
- Mechanisms of interleukin-1beta release.Immunobiology. 2009; 214: 543-553
- Mechanisms of unconventional secretion of IL-1 family cytokines.Cytokine. 2015; 74: 213-218
- Gasdermins: effectors of pyroptosis.Trends Cell Biol. 2017; 27: 673-684
- The inflammasome activating caspase 1 mediates fibrosis and myofibroblast differentiation in systemic sclerosis.Arthritis Rheum. 2011; 63: 3563-3574
- A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases.Nat. Med. 2015; 21: 248-255
- Cathepsin B links oxidative stress to the activation of NLRP3 inflammasome.Exp. Cell Res. 2018; 362: 180-187
- FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation.Nat. Immunol. 2020; 21: 736-745
- Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis.Ann. Rheum. Dis. 2017; 76: 1150-1158
- Changes in macrophage transcriptome associate with systemic sclerosis and mediate GSDMA contribution to disease risk.Ann. Rheum. Dis. 2018; 77: 596-601
- Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.Genome Med. 2020; 12: 81
- Pyroptosis executor gasdermin D plays a key role in scleroderma and bleomycin-induced skin fibrosis.Cell Death Discov. 2022; 8: 183
- The gasdermins, a protein family executing cell death and inflammation.Nat. Rev. Immunol. 2020; 20: 143-157