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Dynein light chain of 8\u2009kDa (LC8) was identified previously as an inhibitor of nuclear factor kappa B (NF\u2010\u03baB), a key regulator of inflammation, however, its role in NASH remains unknown. In this study, we investigated whether LC8 can alleviate NASH using a mouse model of methionine and choline\u2010deficient (MCD) diet\u2010induced NASH and examined the underlying mechanism. LC8 transgenic (Tg) mice showed lower hepatic steatosis and less progression of NASH, including hepatic inflammation and fibrosis, compared to wild\u2010type (WT) mice after consuming an MCD diet. The hepatic expression of lipogenic genes was lower, while that of lipolytic genes was greater in LC8 Tg mice than WT mice, which might be associated with resistance of LC8 Tg mice to hepatic steatosis. Consumption of an MCD diet caused oxidative stress, I\u03baB\u03b1 phosphorylation, and subsequent p65 liberation from I\u03baB\u03b1 and nuclear translocation, resulting in induction of proinflammatory cytokines and chemokines. However, these effects of MCD diet were reduced by LC8 overexpression. Collectively, these results suggest that LC8 alleviates MCD diet\u2010induced NASH by inhibiting NF\u2010\u03baB through binding to I\u03baB\u03b1 to interfere with I\u03baB\u03b1 phosphorylation and by reducing oxidative stress via scavenging reactive oxygen species. Thus, boosting intracellular LC8 could be a potential therapeutic strategy for patients with NASH.<\/jats:p>","DOI":"10.1002\/jcp.30811","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T15:09:43Z","timestamp":1655132983000},"page":"3554-3564","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dynein light chain LC8 alleviates nonalcoholic steatohepatitis by inhibiting NF\u2010\u03baB signaling and reducing oxidative stress"],"prefix":"10.1002","volume":"237","author":[{"given":"Gong\u2010Rak","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Life Science and the Research Center for Cellular Homeostasis Ewha Womans University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye In","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Science and the Research Center for Cellular Homeostasis Ewha Womans 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