| First Author | Sharma A | Year | 2023 |
| Journal | J Cell Physiol | Volume | 238 |
| Issue | 7 | Pages | 1530-1541 |
| PubMed ID | 37098757 | Mgi Jnum | J:359642 |
| Mgi Id | MGI:7788518 | Doi | 10.1002/jcp.31030 |
| Citation | Sharma A, et al. (2023) CD14 is not required for carbon tetrachloride-induced hepatic inflammation and fibrosis with or without lipopolysaccharide challenge. J Cell Physiol 238(7):1530-1541 |
| abstractText | Binding of lipopolysaccharide (LPS) to CD14 is required for its cellular effects via TLR4. A role of LPS/TLR4-mediated signaling in activated hepatic stellate cells (aHSCs), the major fibrogenic cells, in liver fibrosis has been reported. We investigated effects of LPS on carbon tetrachloride (CCl4)-induced fibrosis in CD14-knockout (KO) mice in vivo, and culture-activated HSCs in vitro. CCl4 (biweekly; 4 weeks)-treated wild type (WT) and CD14-KO mice were challenged with single LPS administration for 24 h. Liver injury, inflammation and fibrosis were determined. Culture-activated HSCs from WT or CD14-KO mice were stimulated with LPS. Parameters of fibrogenic activity (expression of collagen1a1 [Col1a1], alpha-smooth muscle actin [alphaSMA] and TGFbeta1) and inflammatory cytokines/chemokines were measured. CCl4 treatment caused similar liver injury and fibrosis in WT and CD14-KO mice. LPS increased liver injury and inflammation similarly in CCl4-treated WT and CD14-KO mice, but downregulated Timp1 and upregulated Mmp13. LPS elicited similar NFkappaB activation and inflammatory response in WT and CD14-KO aHSCs. LPS similarly downregulated Acta2 (encodes alphaSMA), Pdgfrb, Col1a1 and Mmp13 expression but did not affect Timp1 expression in WT and CD14-KO aHSCs. LPS did not alter Tgfb1 but increased expression of decorin (Dcn) (inhibitor of TGFbeta1) expression in WT and CD14-KO aHSCs. The results indicate that the effects of LPS on HSCs are CD14-independent, and CD14 is not required for hepatic fibrosis. LPS-induced down-modulation of fibrogenic markers in aHSCs is also CD14-independent. |
