Toll like receptor 2 knock‐out attenuates carbon tetrachloride (CCl4)‐induced liver fibrosis by downregulating MAPK and NF‐κB signaling pathways. Issue 12 (8th May 2014)

• Record Type: Journal Article
• Authors: Ji, Lingling; Xue, Ruyi; Tang, Wenqing; Wu, Weibin; Hu, Tingting; Liu, Xijun; Peng, Xiaomin; Gu, Jianxin; Chen, She; Zhang, Si
• Is Part Of: FEBS letters. Volume 588:Issue 12(2014)
• Page Start: 2095
• Page End: 2100
• Publication Date: 2014-05-08
• Subjects: CCl4 -- carbon tetrachloride -- α-SMA -- smooth muscle alpha-actin -- WT -- wild-type -- TGF -- transforming growth factor -- Col1A1 -- type I procollagen α1 chain -- TLR -- Toll like receptor -- TBIL -- total bilirubin -- ALP -- alkaline phosphatase -- MAPK -- mitogen-activated protein kinases -- IL -- interleukin -- NF-κB -- nuclear factor kappa B -- TNF -- tumor necrosis factor -- H&E -- hematoxylin and eosin -- HSC -- hepatic stellate cell -- ERK -- extracellular signal-regulated kinase -- JNK -- c-Jun N-terminal kinase -- ECM -- extracellular matrix proteins -- PDGF -- platelet-derived growth factor -- PAMP -- pathogen-associated molecular patterns -- DAMP -- damage-associated molecular patterns -- LTA -- lipoteichoic acid -- Liver fibrosis -- Toll like receptor 2 -- Carbon tetrachloride -- Hepatic stellate cell -- mitogen-activated protein kinases -- NF-κB; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.04.042
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Innate immune signaling associated with Toll‐like receptors (TLRs) is a key pathway involved in the progression of liver fibrosis. In this study, we reported that TLR2 is required for hepatic fibrogenesis induced by carbon tetrachloride (CCl4 ). After CCl4 treatment, TLR2 −/− mice had reduced liver enzyme levels, diminished collagen deposition, decreased inflammatory infiltration and impaired activation of hepatic stellate cells (HSCs) than wild type (WT) mice. Furthermore, after CCl4 treatment, TLR2 −/− mice demonstrated downregulated expression of profibrotic and proinflammatory genes and impaired mitogen‐activated protein kinases (MAPK) and nuclear factor kappa B (NF‐κB) activation than WT mice. Collectively, our data indicate that TLR2 deficiency protects against CCl4 ‐induced liver fibrosis. Abstract : CCl4 ‐induced elevation of serum ALP and TBIL was reduced in TLR2 −/− mice. CCl4 ‐induced liver collagen deposition was attenuated in TLR2 −/− mice. CCl4 ‐induced inflammatory response was ameliorated in TLR2 −/− mice. CCl4 ‐induced activation of MAPK and NF‐κB signaling pathways was attenuated in TLR2 −/− mice.