In conclusion, our findings suggest that RIP3 plays a crucial proinflammatory role in liver fibrosis by regulating the ROCK1-TLR4-NF-κB signaling pathway in macrophages and therefore may be a potential therapeutic target for immune-mediated liver fibrosis.-Wei, S., Zhou, H., Wang, Q., Zhou, S., Li, C., Liu, R., Qiu, J., Shi, C., Lu, L. RIP3 deficiency alleviates liver fibrosis by inhibiting ROCK1-TLR4-NF-κB pathway in macrophages.
The inhibition of tTG activity through cystamine administration or gene knockout alleviated the level of TLR4, NF-κB pathway molecules, IL-33/ST2, and the severity of liver fibrosis resulting from Sj infection.
Toll-like receptor 2 (TLR2) and TLR4 are pattern recognition receptors of bacterial lipoprotein and lipopolysaccharide, both of which participate in activating hepatic stellate cells and liver fibrosis.
This study demonstrates that Toll-like receptors 4 (TLR4)/nuclear factor kappa B (NF-κB) signal is an important regulator of liver fibrosis while TLR4/NF-κB mRNA and protein levels reduced during HSCs activation.
Sparstolonin B (SsnB) attenuates liver fibrosis via a parallel conjugate pathway involving P53-P21 axis, TGF-beta signaling and focal adhesion that is TLR4 dependent.
These results demonstrate that Andro prevents liver inflammation and fibrosis, which is in correlation with the inhibition of the TGF-<i>β</i>1/Smad2 and TLR4/NF-<i>κ</i>B p50 pathways, highlighting Andro as a potential therapeutic strategy for liver fibrosis.
The results provide evidence of the TLR4/LPS-independent mechanisms of liver fibrosis and also indicate that TLR4 is not entirely critical to LPS-induced acute liver injury.
Recent studies show that TLR4 plays an important role in several other types of liver fibrosis, but the mechanism of TLR4 in PABF is yet really unclear.
In summary, our study demonstrates that LPS- and TNF-α-induced NF-κBp50-HDAC1 interaction represses BAMBI transcriptional activity, which contributes to TLR4-mediated enhancement of TGF-β signaling in HSCs during liver fibrosis.
Lipopolysaccharide (LPS)-mediated signaling through Τoll-like receptor 4 (TLR4) in HSCs has been identified as a key event in liver fibrosis, and as the molecular link between inflammation and liver fibrosis.
ACAT1-deficient and wild-type mice, or Toll-like receptor 4 (TLR4)(-/-)ACAT1(+/+) and TLR4(-/-)ACAT1(-/-) mice were subjected to bile duct ligation (BDL) for 3 weeks or were given carbon tetrachloride (CCl4) for 4 weeks to induce liver fibrosis.
A recent study reported that TLR4 gene polymorphisms are good prognostic predictors and are associated with protection from liver fibrosis among Caucasians.
At stepwise logistic regression analysis, the carriage of TLR-4rs4986790 A/A genotype was found to be and independent predictor of liver fibrosis (O.R.14.8, p = 0.019).
Intestinal decontamination inhibits TLR4 dependent fibronectin-mediated cross-talk between stellate cells and endothelial cells in liver fibrosis in mice.
While studies in animal models have linked Toll-like receptor (TLR) 4 signaling to the pathophysiology of ischemia/reperfusion (IR) injury and liver fibrosis, the relevance of TLR4 activation after human liver transplantation is unknown.
The finding was strengthened by the strong association of TLR4 polymorphism with liver fibrosis in the subgroup of 52 patients who underwent a liver biopsy (P = 0.011).
Since TLR4 mutant mice are resistant to liver fibrosis, the TLR4/MD2 soluble receptor might represent a new therapeutic molecule for liver fibrogenesis in vivo.