Modulation of Non-Alcoholic Steatohepatitis by Pattern Recognition Receptors in Mice: The Role of Toll-Like Receptors 2 and 4
Article first published online: 3 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 29, Issue Supplement s2, pages 140S–145S, November 2005
How to Cite
Szabo, G., Velayudham, A., Romics, L. and Mandrekar, P. (2005), Modulation of Non-Alcoholic Steatohepatitis by Pattern Recognition Receptors in Mice: The Role of Toll-Like Receptors 2 and 4. Alcoholism: Clinical and Experimental Research, 29: 140S–145S. doi: 10.1097/01.alc.0000189287.83544.33
- Issue published online: 3 MAY 2006
- Article first published online: 3 MAY 2006
- Received for publication January 24, 2005; accepted June 24, 2005.
- Toll-Like Receptors;
Abstract: Toll-like receptors (TLR) recognize pathogen-derived molecules and induce downstream activation of inflammatory pathways. Fatty liver has been shown to result in increased sensitivity to lipopolysaccharide (LPS), a TLR4 ligand. In this study, we investigated the roles of TLR2 and TLR4 in liver damage and on cytokine induction in a methionine-choline deficient (MCD) diet-induced model of nonalcoholic steatohepatitis. We found that mice with nonalcoholic fatty liver had increased liver injury and inflammatory cytokine induction after challenge with a TLR4 but not with a TLR2 ligand. TLR2 deficient mice were not protected against the development of steatohepatitis after MCD diet feeding. On the contrary, TLR2−/− mice had significantly higher levels of serum ALT and greater TNF-α levels after LPS challenge suggesting increased liver injury. This was associated with reduced production of IL-6, a cytokine with hepatoprotective effects in fatty liver. Increased liver injury in the MCD diet-fed TLR2−/− mice was associated with reduced baseline and LPS-induced NF-kB and PPRE binding compared to MCS controls. These results demonstrate that TLR2 deficiency results in increased liver injury in association with nonalcoholic steatohepatitis and may suggest a protective role for TLR2-mediated signals in liver injury.