Bay11-7082 attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-¦ÊB activation

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• 作者：Jijun Zhao ; Hui Zhang ; Yuefang Huang ; Hongyue Wang ; Shuang Wang ; Chunmei Zhao ; Yingjie Liang ; Niansheng Yang
• 关键词：Lupus nephritis ; Bay11-7082 ; NF-¦ÊB ; NLRP3 inflammasome
• 刊名：International Immunopharmacology
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：17
• 期：1
• 页码：116-122
• 全文大小：1118 K

文摘

Nuclear factor-kappa B (NF-¦ÊB) and NLRP3 inflammasome are involved in inflammation and autoimmunity. In vitro data have shown that Bay11-7082 selectively inhibits NLRP3 inflammasome activity independent of NF-¦ÊB activity. In this study, we evaluated the therapeutic effects of Bay11-7082 on murine lupus nephritis (LN) in vivo. Twelve-week-old MRL/lpr mice were treated with either Bay11-7082 (5 mg/kg) or vehicle (DMSO/PBS buffer) by intraperitoneal injection thrice per week for 8 weeks. NLRP3 inflammasome formation and NF-¦ÊB activation were measured. Histopathology, immune complex deposits, proteinuria, renal function and production of anti-dsDNA antibody as well as inflammatory markers were evaluated. Bay11-7082 treatment inhibited renal NLRP3 inflammasome formation and NF-¦ÊB activation in vivo. Bay11-7082 decreased proteinuria, blood urea nitrogen, resulting in dramatically attenuated renal damage. Bay11-7082-treated mice had decreased serum anti-dsDNA level and less renal immune complex deposition. The IL-1¦Â, TNF-¦Á and chemokine (C-C Motif) ligand 2 (CCL2) levels and infiltration of macrophages as well as the mortality were significantly reduced by Bay11-7082 treatment. This study suggests that dual inhibition of NLRP3 inflammasome and NF-¦ÊB activation using Bay11-7082 or its analogues may be a promising therapeutic strategy for preventing the progression of LN.