Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 20, Issue 1, Pages 24-32Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2014.02.017
Keywords
Home oxygenase-1; NLRP3 inflammasome; Sepsis; Acute lung injury
Categories
Funding
- National Natural Scientific Foundation of China [81171785]
- Natural Scientific Foundation of Heilongjiang Provinc [ZJYO704-02]
- Scientific Research Fund of Heilongjiang Provincial Education Department [12521214]
- Youth Scientific Foundation of Heilongjiang Province [QC2012C014]
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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. (C) 2014 Elsevier B.V. All rights reserved.
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