Autoimmune hepatitis (AIH) is a progressive inflammatory disorders of unknown etiology, characterized by immune-mediated destruction of hepatocytes and massive production of cytokines. Interleukin-1β is a pleiotropic proinflammatory cytokine and well known to be critical in a variety of autoimmune diseases. However, the role of interleukin-1β (IL-1β) in AIH is still indistinct. Here, we first investigated the significance of NOD-like receptor protein 3 (NLRP3) inflammasome-dependent IL-1β in the pathogenesis of AIH with a murine model of immune-mediated hepatitis induced by Concanavalin A (ConA). In ConA-treated mice, pathogenic elevated NLRP3, Cleaved caspase-1 and IL-1β levels, as well as an inflammatory cell death known as pyroptosis predominantly occurred in the livers. Strikingly, NLRP3-/- and caspase-1-/- mice were broadly protected from hepatitis as determined by decreased histological liver injury, serum aminotransferase (ALT)/aspartate transaminase levels, and pyroptosis. In vivo intervention with recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) strongly suppressed ConA-induced hepatitis by decreasing tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) secretion, and inflammatory cell infiltration into livers. Additionally, rhIL-1Ra-pretreated mice developed significantly reduced NLRP3 inflammasome activation and reactive oxygen species (ROS) generation. Scavenging of ROS by N-acetyl-cysteine also attenuated NLRP3 inflammasome activation and liver inflammation, indicating that the essential role of ROS in mediating NLRP3 inflammasome activation in ConA-induced hepatitis. In conclusion, our results demonstrated that NLRP3 inflammasome-dependent IL-1β production was crucial in the pathogenesis of ConA-induced hepatitis, which shed light on the development of promising therapeutic strategies for AIH by blocking NLRP3 inflammasome and IL-1β.
文章引用产品列表
-
- EK282
- ELISA试剂盒
Mouse TNF-a ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00
-
- EK282HS
- 高敏试剂盒
Mouse TNF-α High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK222
- ELISA试剂盒
Mouse IL-22 ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥2,650.00
-
- EK222HS
- 高敏试剂盒
Mouse IL-22 High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK218
- ELISA试剂盒
Mouse IL-18 ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥2,650.00
-
- EK217HS
- 高敏试剂盒
Mouse IL-17A High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK217
- ELISA试剂盒
Mouse IL-17A ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥2,650.00
-
- EK201BHS
- 高敏试剂盒
Mouse IL-1β High Sensitivity ELISA Kit检测试剂盒(酶联免疫吸附法)
- ¥2,000.00 – ¥3,400.00
-
- EK201B
- ELISA试剂盒
Mouse IL-1β ELISA Kit 检测试剂盒(酶联免疫吸附法)
- ¥1,600.00 – ¥10,800.00