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Background Activation of the NLRP3 inflammasome in gout amplifies the inflammatory response and mediates further damage. In the current study, we assessed the therapeutic effect of OLT1177, an orally active NLRP3 inflammasome inhibitor that is safe in humans, in murine acute arthritis models. Methods Zymosan or monosodium urate (MSU) crystals were injected intra-articularly (i.a.) into mouse knee...
IL-1 family member IL-37 inhibits a broad spectrum of inflammatory assaults in cell lines and primary PBMC; in vivo, mice transgenic for IL-37 (IL-37tg) exhibit markedly reduced manifestations of LPS-induced shock, DSS colitis, antigen-specific immune responses and ischemia–reperfusion injury. Although previous studies reported that recombinant IL-37 associates with the IL-18 receptor alpha chain...
IL-1 family member IL-37 reduces innate inflammation and acquired immune responses. Our published studies demonstrated that over expression of IL-37 in either primary or transfected cell line cultures suppress the production of pro-inflammatory cytokines induced by Toll-like receptor ligands, IL-1b or TNFa. Inhibition of endogenous IL-37 in human monocytes increases IL-1b production. Similar to IL-1...
Although often studied for its ability to inhibit neutrophil elastase, alpha-1 antitrypsin (AAT) has broad anti-inflammatory properties not related to its anti-protease activity. For example, monotherapy of mice with human plasma-derived AAT prevents pancreatic islet beta cell allograft rejection, the incidence of diabetes in the NOD mouse, DSS colitis, ischemia–reperfusion injury in the heart and...
Targeting major proinflammatory cytokines such as IL-1β and TNFα is of great interest in patients with chronic inflammatory diseases, including rheumatoid arthritis, colitis, and psoriasis. The cytokine Interleukin (IL)-32 induces proinflammatory cytokines such as TNFα, IL-1β, IL-6, and chemokines. We previously used an IL-32 ligand-affinity column to purify proteinase 3, which is abundantly expressed...
Interleukin (IL)-32 was recently identified as a new cytokine which induces various proinflammatory cytokines in human monocytes and macrophages. Therefore, IL-32 has been primarily studied in inflammatory models such as rheumatoid arthritis and inflammatory bowel diseases. The regulation of endogenous IL-32 in other immune cells remains unknown. In the present study, we stimulated Jurkat T cells...
We describe the gene structure, regulation, signal transduction. and functions of a cytokine, interleukin (IL)-32. An IL-18 unresponsive cell was converted to a responsive cell by transfection of the IL-18 receptor β chain, and IL-18-induced microarray revealed high expression of a cytokine-like gene. Although IL-32 does not share sequence homology with known cytokine families, IL-32 induces various...
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