Loss of toll-like receptor 3 aggravates hepatic inflammation but ameliorates steatosis in mice

Young-Sun Lee, Do Yeon Kim, Tae Jun Kim, So Yeon Kim, Jong Min Jeong, Won Il Jeong, Jae Kwang Jung, Jae Kap Choi, Hyon Seung Yi, Jin Seok Byun

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The importance of toll-like receptor (TLR) 4 in the pathogenesis of steatohepatitis has been well documented; however, little is known about the role of TLR3. In this study, we determined whether the depletion of TLR3 modulated hepatic injury in mice and further aimed to provide mechanistic insights into the TLR3-mediated modulation of diet-induced hepatic inflammation and fat accumulation. Hepatic steatosis and inflammatory response were induced by feeding wild-type (WT) or TLR3 knockout mice a high-fat diet for 8 weeks. Primary liver resident cells, including hepatocytes, Kupffer cells, and hepatic stellate cells (HSCs), were treated with palmitic acid. TLR3 knockout mice fed a high-fat diet showed severe hepatic inflammation accompanied by nuclear factor-κB and IRF3 activation, which is mainly induced by the activation of Kupffer cells. Decreased TLR4 expression was restored in hepatic mononuclear cells and Kupffer cells in TLR3 knockout mice compared to that in the WT. Moreover, hepatic steatosis was decreased in TLR3 knockout mice. Hepatocytes from TLR3 knockout mice exhibited reduced expression of cannabinoid receptors. HSCs from TLR3 knockout mice showed decreased expression of the enzymes involved in endocannabinoid synthesis. In conclusion, this study suggests that the selective modulation of TLR3 could be a novel therapeutic target for the treatment of hepatic inflammation and steatosis.

Original languageEnglish
Pages (from-to)957-962
Number of pages6
JournalBiochemical and biophysical research communications
Volume497
Issue number4
DOIs
Publication statusPublished - 2018 Mar 18

Keywords

  • Endocannabinoids
  • Lipogenesis
  • Necroinflammations
  • Nonalcoholic steatohepatitis

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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