Incidence of nonalcoholic fatty liver disease is increasing worldwide. Activation of the NLRP3 inflammasome is central to the development of diet-induced nonalcoholic steatohepatitis (NASH). We investigated whether benzyl isothiocyanate (BITC) ameliorates diet-induced NASH and the mechanisms involved. C57BL/6 J mice fed a high-fat diet containing cholesterol and cholic acid (HFCCD) and Kupffer cells stimulated with LPS and cholesterol crystals (CC) were studied. LPS/CC increased the expression of the active form of caspase 1 (p20) and the secretion of IL-1β by Kupffer cells, and these changes were reversed by MCC950, an NLRP3 inflammasome inhibitor. LPS/CC-induced NLRP3 inflammasome activation and IL-1β production were dose-dependently attenuated by BITC. BITC decreased cathepsin B release from lysosomes and binding to NLRP3 induced by LPS/CC. Compared with a normal diet, the HFCCD increased serum levels of ALT, AST, total cholesterol, and IL-1β and hepatic contents of triglycerides and total cholesterol. BITC administration (0.1% in diet) reversed the increase in AST and hepatic triglycerides in the HFCCD group. Moreover, BITC suppressed lipid accumulation, macrophage infiltration, fibrosis, crown-like structure formation, and p20 caspase 1 and p17 IL-1β expression in liver in the HFCCD group. These results suggest that BITC ameliorates HFCCD-induced steatohepatitis by inhibiting the activation of NLRP3 inflammasome in Kupffer cells and may protect against diet-induced NASH.

中文翻译：

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异硫氰酸苄酯通过抑制Kupffer细胞中胆固醇晶体激活的NLRP3炎性体，改善了高脂/胆固醇/胆酸饮食诱导的非酒精性脂肪性肝炎。

全球非酒精性脂肪肝的发病率正在上升。NLRP3炎性小体的激活对于饮食诱导的非酒精性脂肪性肝炎（NASH）的发展至关重要。我们调查了异硫氰酸苄酯（BITC）是否能改善饮食引起的NASH及其机制。研究了以高脂饮食喂养的含有胆固醇和胆酸（HFCCD）的C57BL / 6 J小鼠以及LPS和胆固醇晶体（CC）刺激的库普弗细胞的研究。LPS / CC增加了Cupase 1（p20）活性形式的表达和库普弗细胞分泌的IL-1β，这些变化被NLRP3炎性体抑制剂MCC950逆转。LPS / CC诱导的NLRP3炎性小体激活和IL-1β产生被BITC剂量依赖性地减弱。BITC减少了组织蛋白酶B从溶酶体的释放，并与LPS / CC诱导的NLRP3结合。与正常饮食相比，HFCCD可提高血清ALT，AST，总胆固醇和IL-1β的含量，并增加甘油三酸酯和总胆固醇的肝脏含量。在HFCCD组中，BITC的使用（饮食的0.1％）逆转了AST和肝甘油三酸酯的增加。此外，在HFCCD组中，BITC抑制了肝脏中的脂质蓄积，巨噬细胞浸润，纤维化，冠状结构形成以及p20 caspase 1和p17IL-1β的表达。这些结果表明，BITC通过抑制Kupffer细胞中NLRP3炎性小体的活化来改善HFCCD诱导的脂肪性肝炎，并且可以预防饮食引起的NASH。1％的饮食）逆转了HFCCD组AST和肝甘油三酯的增加。此外，在HFCCD组中，BITC抑制了肝脏中的脂质蓄积，巨噬细胞浸润，纤维化，冠状结构形成以及p20 caspase 1和p17IL-1β的表达。这些结果表明，BITC通过抑制Kupffer细胞中NLRP3炎性小体的活化来改善HFCCD诱导的脂肪性肝炎，并且可以预防饮食引起的NASH。1％的饮食）逆转了HFCCD组AST和肝甘油三酸酯的增加。此外，在HFCCD组中，BITC抑制了肝脏中的脂质蓄积，巨噬细胞浸润，纤维化，冠状结构形成以及p20 caspase 1和p17IL-1β的表达。这些结果表明，BITC通过抑制Kupffer细胞中NLRP3炎性小体的活化来改善HFCCD诱导的脂肪性肝炎，并且可以预防饮食引起的NASH。