Toll-like receptor 2 signaling in liver pathophysiology

• Published in: Life sciences (1973) Vol. 284; p. 119941
• Main Authors: Getachew, Anteneh, Hussain, Muzammal, Huang, Xinping, Li, Yinxiong
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.11.2021; Elsevier BV
• Subjects: Abuse; adults; alcohol abuse; Antigens; Cancer; Cirrhosis; Crosstalk; Cytokines; disease progression; Drug abuse; Fibrosis; Hepatitis; Hepatocytes; High fat diet; HSCs; Inflammation; KCs; Kupffer cells; Liver; Liver cirrhosis; Liver diseases; Morbidity; mortality; Pathogenesis; pathophysiology; Signal transduction; Signaling; Stellate cells; Therapeutic targets; therapeutics; TLR2; TLR2 protein; Toll-like receptor 2; Toll-like receptors; viruses; HSCs; KCs; Inflammation; Fibrosis; TLR2; Cancer
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2021.119941

Chronic liver diseases (CLD) are among the major cause of mortality and morbidity worldwide. Despite current achievements in the area of hepatitis virus, chronic alcohol abuse and high-fat diet are still fueling an epidemic of severe liver disease, for which, an effective therapy has yet not been discovered. In particular, the therapeutic regimens that could prevent the progression of fibrosis and, in turn, aid cirrhotic liver to develop a robust regenerative capability are intensively needed. To this context, a better understanding of the signaling pathways regulating hepatic disease development may be of critical value. In general, the liver responds to various insults with an orchestrated healing process involving variety of signaling pathways. One such pathway is the TLR2 signaling pathway, which essentially regulates adult liver pathogenesis and thus has emerged as an attractive target to treat liver disease. TLR2 is expressed by different liver cells, including Kupffer cells (KCs), hepatocytes, and hepatic stellate cells (HSCs). From a pathologic perspective, the crosstalk between antigens and TLR2 may preferentially trigger a distinctive set of signaling mechanisms in these liver cells and, thereby, induce the production of inflammatory and fibrogenic cytokines that can initiate and prolong liver inflammation, ultimately leading to fibrosis. In this review, we summarize the currently available evidence regarding the role of TLR2 signaling in hepatic disease progression. We first elaborate its pathological involvement in liver-disease states, such as inflammation, fibrosis, and cirrhosis. We then discuss how therapeutic targeting of this pathway may help to alleviate its disease-related functioning. [Display omitted] •TLR2 is expressed both in parenchymal and non-parenchymal hepatic cells.•TLR2 is a crucial receptor that promotes liver injury, inflammation, and fibrosis.•TLR2 signaling is subject to multilayer regulatory control mechanisms.•TLR2 contributes to the development of NASH and ALD.