Hemin inhibits NLRP3 inflammasome activation in sepsis-induced acute lung injury, involving heme oxygenase-1

作者：Luo, Yun-peng; Jiang, Lei; Kang, Kai; Fei, Dong-sheng; Meng, Xiang-lin; Nan, Chuan-chuan; Pan, Shang-ha; Zhao, Ming-ran; Zhao, Ming-yan^*

来源：International Immunopharmacology, 2014, 20(1): 24-32.

DOI：10.1016/j.intimp.2014.02.017

• Home oxygenase-1
• NLRP3 inflammasome
• Sepsis
• Acute lung injury

NLRP3 inflammasome activation contributes to acute lung injury (ALI), accelerating caspase-1 maturation, and resulting in IL-I beta and IL-18 over-production. Home oxygenase-1 (HO-1) plays a protective role in ALI. This study investigated the effect of hemin (a potent HO-1 inducer) on NLRP3 inflammasome in sepsis-induced ALL. The sepsis model of cecal ligation and puncture (CLP) was used in C57BL6 mice. In vivo induction and suppression of HO-1 were performed by pretreatment with hemin and zinc protoporphyrin IX (ZnPP, a HO-1 competitive inhibitor) respectively. CLP triggered significant pulmonary damage, neutrophil infiltration, increased levels of IL-1 beta and IL-18, and edema formation in the lung. Hemin pretreatment exerted inhibitory effect on lung injury and attenuated IL-1 beta and IL-18 secretion in serum and lung tissue. In lung tissues, hemin down-regulated mRNA and protein levels of NLRP3, ASC and caspase-1. Moreover, hemin reduced malondialdehyde and reactive oxygen species production, and inhibited NF-kappa B and NLRP3 inflammasome activity. Meanwhile, hemin significantly increased HO-1 mRNA and protein expression and HO-1 enzymatic activity. In contrast, no significant differences were observed between the CLP and ZnPP groups. Our study suggests that hemin-inhibited NLRP3 inflammasome activation involved HO-1, reducing IL-1 beta and IL-18 secretion and limiting the inflammatory response.

• 出版日期2014-5
• 单位哈尔滨医科大学