Nucleotide binding and oligomerization domain like receptors (NLR) inflammasomes in patients with non-alcoholic fatty liver disease (NAFLD)

Abstract

Background Inflammasomes, pro-caspase-1 containing multiprotein complex which is critical for activating key pro-inflammatory cytokines, have an important role in the onset and progression of chronic liver disease. Aims of our study were to measure the NLRs expression and define the role of NLRs in patients with NAFLD.

Methods Human liver tissues and serum sample from patients with NAFLD were collected. Control samples that had pathologically fatty change less than 5% were obtained from liver transplantation donor. Relative mRNA levels of NLRP3, NLRP6 and NLRP10, IL-1beta and caspase-1 of pro-inflammatory cytokines were analyzed. Also, we analyzed the protein expression of NLRs in human serum by western blot analysis.

Results When we compared the liver tissue mRNA of NLRs including NLRP3, NLRP6 and NLRP10 in NAFLD (n=14) with controls (n=12), NLRP3 (NAFLD vs. controls, 82.8-fold) and NLRP 10 (127.5-fold) were significantly increased in NAFLD (all p <0.05). Also, serum AST and ALT levels were significantly elevated in NAFLD (AST, 96.8 ± 55.8; ALT, 170.7 ±120.1) compared with the control (AST, 17.9 ± 5.3; ALT, 13.8 ± 6.4) group (p <0.05). Caspase-1 in liver tissue were significantly increased in NAFLD (10.5-fold, p<0.05). Finally, IL-1beta inflammatory cytokine was significantly increased in NAFLD (8.0-fold, p<0.05) relative to control group. In addition to liver tissue samples, NLRP3 protein expression in the serum samples from patients with NAFLD (n=24) were significantly elevated compared with controls (n=19) (NAFLD vs. controls 3.0-fold).

Conclusions Using human liver tissue and serum samples from NAFLD, our study demonstrated the important role of inflammasomes in NAFLD. In addition to NLRP3 which is known to be essential to initiate adaptive immune response by dendritic cell, NLRP 10 might have an important role in the pathogenesis of NAFLD.