The involvement of NLRX1 and NLRP3 in the development of nonalcoholic steatohepatitis in mice

Abstract

BackgroundIncreasing evidence suggests that innate immunity is involved in the development of nonalcoholic fatty liver disease. Nod-like receptors (NLRs) have recently been identified as key mediators of inflammatory and immune responses. The aim of this article is to explore the correlation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)X1 and NLRP3 with nonalcoholic steatohepatitis (NASH) in mice. MethodsIn our study, a high-fat diet, lipopolysaccharides (LPSs), and normal diet were given to C57BL mice to establish high fat (HF), HF + LPS, and control groups. Thereafter, serum alanine and aspartate aminotransferase (ALT and AST) levels were measured, and NASH severity was histologically examined. We measured tumor necrosis factor (TNF)-α levels by enzyme-linked immunosorbent assay, protein expression by Western blotting, and mRNA expression by real-time fluorescent quantitative reverse transcription-polymerase chain reaction. ResultsLevels of ALT and AST were higher in HF + LPS mice than in HF mice (p < 0.05). NLRX1 mRNA and protein expression was lower in HF and HF + LPS mice than in control mice (⤳ < 0.05). NLRP3 mRNA expression was higher in HF and HF + LPS mice than in control mice (⤳ < 0.05). The mRNA and protein expression of TNF receptor-associated factor (TRAF)6, interleukin-1β, caspase-1, and apoptosis-associated speck-like protein were significantly higher in HF + LPS mice than in control and HF mice; furthermore, mRNA expression was higher in HF mice than in control mice (⤳ < 0.05), but protein expression was similar. ConclusionNLRX1 and NLRP3 inflammasomes may be important in NASH development.