Alcohol-Induced Liver Injury Is Modulated by Nlrp3 and Nlrc4 Inflammasomes in Mice

被引：58

作者：

DeSantis, David A. ^{[1
]}

Ko, Chih-wei ^{[1
]}

Liu, Yang ^{[1
]}

Liu, Xiuli ^{[2
]}

Hise, Amy G. ^{[3
,4
,5
]}

Nunez, Gabriel ^{[6
]}

Croniger, Colleen M. ^{[1
]}

机构：

[1] Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH 44106 USA

[2] Cleveland Clin, Dept Anat Pathol, Cleveland, OH USA

[3] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA

[4] Louis Stokes Cleveland Dept Vet Affairs Med Ctr, Dept Med, Cleveland, OH 44106 USA

[5] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA

[6] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

来源：

MEDIATORS OF INFLAMMATION | 2013年 / 2013卷

关键词：

NF-KAPPA-B; DIET-INDUCED OBESITY; CELL-DEATH; ACTIVATES CASPASE-1; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; KUPFFER CELLS; PROGRESSION; CYTOKINES; INTERLEUKIN-1-BETA;

D O I：

10.1155/2013/751374

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Alcoholic liver disease (ALD) is characterized by increased hepatic lipid accumulation (steatosis) and inflammation with increased expression of proinflammatory cytokines. Two of these cytokines, interleukin-1 beta (IL-1 beta) and IL-18, require activation of caspase-1 via members of the NOD-like receptor (NLR) family. These NLRs form an inflammasome that is activated by pathogens and signals released through local tissue injury or death. NLR family pyrin domain containing 3 (Nlrp3) and NLR family CARD domain containing protein 4 (Nlrc4) have been studied minimally for their role in the development of ALD. Using mice with gene targeted deletions for Nlrp3 (Nlrp3(-/-)) and Nlrc4 (Nlrc4(-/-)), we analyzed the response to chronic alcohol consumption. We found that Nlrp3(-/-) mice have more severe liver injury with higher plasma alanine aminotransferase (ALT) levels, increased activation of IL-18, and reduced activation of IL-1B. In contrast, the Nlrc4(-/-) mice had similar alcohol-induced liver injury compared to C57BL/6J (B6) mice but had greatly reduced activation of IL-1 beta. This suggests that Nlrp3 and Nlrc4 inflammasomes activate IL-1 beta. and IL-18 via caspase-1 in a differential manner. We conclude that the Nlrp3 inflammasome is protective during alcohol-induced liver injury.

引用

页数：12

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