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- Hepatic fibrosis
- chronic liver disease¸liver
- immunology in hepatology
- liver cirrhosis
- molecular genetics
Most types of chronic liver disease are characterised by hepatocellular necrosis, inflammation and tissue remodelling, ultimately resulting in progressive fibrosis and cirrhosis in a significant number of cases. Evidence from mouse and human studies implicates Toll-like receptors (TLRs) as central mediators of the inflammatory response and a crucial link between inflammation and fibrosis in chronic liver diseases. TLRs are members of the pattern-recognition receptor superfamily, which plays an important role in pathogen recognition and the subsequent activation of the innate immune system.1 To date, 10 functional TLRs have been identified in humans and each of these responds to specific microbial products. TLR4 is the main receptor for lipopolysaccharide, which appears to be a key mediator of liver inflammation associated with several different liver diseases.2 ,3 The interaction of TLR4 with lipopolysaccharide, a specific cell wall component of Gram-negative bacteria, leads to liver fibrosis triggered by proinflammatory cytokines, transforming growth factor β signalling and oxidative stress.4 Notably, TLR4 may also recognise endogenous ligands released by activated or necrotic cells during tissue injury and matrix degradation.3 Within the liver, TLR4 is expressed on diverse cell types, including Kupffer cells (KCs), hepatic stellate cells and hepatocytes (figure 1).5 Activation of TLR4 directly stimulates stellate …
Footnotes
Funding Work in the lab of H E Wasmuth is supported by grants from the Deutsche Forschungsgemeinschaft (WA 2557/2-1 and SFB/TRR 57 P08) and the Else Kröner-Fresenius Stiftung.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.