Palmitic acid stimulates NLRP3 inflammasome activation through TLR4-NF-κB signal pathway in hepatic stellate cells.

Abstract

BACKGROUND:

The NLRP3 inflammasome activation plays an important role in the development of NASH and fibrogenesis. However, the mechanisms involved in NLRP3 activation in hepatic stellate cells (HSCs) have been unclear. The aim of this study was to investigate the mechanism of NLRP3 activation in HSCs and the role of NLPR3 inflammasome activation in HSCs on the development of nonalcoholic steatohepatitis (NASH) to fibrosis.

METHODS:

Primary HSCs isolated from SD rats were incubated with palmitic acid and/or LPS, respectively. For in vivo animal experiment, 4-week-old SD rats were fed with high fat diet (HF-diet) for 12 weeks, SD rats were sacrificed at 0, 4, 8 and 12 w. In another group of animal experiment, 4-week-old SD rats were fed with HF-diet and a NLRP3 inhibitor (intraperitoneal injection of NLRP3 inhibitor glybenclamide 5 mg/kg, injected every 3 days) for 12 weeks. Liver tissue and serum were harvested. RT-PCR, WB, ELISA, immunofluorescence and immunohistochemistry were performed to assess the NLRP3 inflammasome activation and signal molecules.

RESULTS:

Palmitic acid stimulated NLPR3 inflammasome activation and fibrotic phenotype change in primary HSCs, LPS sensitizes the response of HSCs to palmitic acid. TLR4-NF-κB signal pathway was involved in NLRP3 inflammasome activation in palmitic acid-exposed HSCs and HF diet-induced NASH. It is evident that administration of NLRP3 inhibitor reduced the development of NASH to liver fibrosis in the NASH rat model.

CONCLUSIONS:

Palmitic acid stimulates NLRP3 inflammasome activation through the TLR4-NF-κB signal pathway in HSCs. NLRP3 inflammasome activation in HSCs exacerbates the development of NASH to liver fibrosis.

• Authors: Zhixia Dong, Qian Zhuang, Min Ning, Shan Wu, Lungen Lu, Xinjian Wan
• Journal: Annals of translational medicine (Ann Transl Med) Vol. 8 Issue 5 Pg. 168 (Mar 2020) ISSN: 2305-5839 [Print] China
• PMID: 32309315 (Publication Type: Journal Article)
• Copyright: 2020 Annals of Translational Medicine. All rights reserved.