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Atherogenic diet‐induced hepatitis is partially dependent on murine TLR4
Author(s) -
Desai Moreshwar S.,
Mariscalco M. Michele,
Tawil Ahmad,
Vallejo J. G.,
Smith C. W.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0607390
Subject(s) - steatosis , biology , medicine , endocrinology , tlr4 , inflammation , alanine transaminase , proinflammatory cytokine , fatty liver , fibrosis , chemokine , liver injury , immunology , disease
Diets high in cholesterol and cholate such as the Paigen diet have been used to study atherogenesis, lithogenesis, and proinflammatory microvascular changes induced by nutritional hypercholesterolemia. Although these diets lead to chronic hepatic inflammation and fibrosis, the early inflammatory changes have been poorly characterized. TLR4, a known receptor for LPS, is also a receptor for a variety of endogenous ligands and has been implicated in atheroma formation. Here, we specifically examined the early inflammatory response of the liver to the atherogenic (ATH) diet and the possible contribution of TLR4. Animals fed the high‐cholesterol/cholate diet for 3 weeks developed a significant, predominantly mononuclear leukocyte infiltration in the liver, hepatic steatosis, elevated hepatic expression of MCP‐1, RANTES, and MIP‐2, and increased serum levels of liver enzymes. In TLR4‐deleted animals, there was a 30% attenuation in the serum alanine transaminase levels and a 50% reduction in the leukocyte infiltration with a fourfold reduction in chemokine expression. In contrast, hepatic steatosis did not differ from wild‐type controls. TLR2 deletion had no effect on diet‐induced hepatitis but increased the amount of steatosis. We conclude that the early inflammatory liver injury but not hepatic lipid loading induced by the ATH diet in mice is mediated in part by TLR4.