Article: Atherogenic diet-induced hepatitis is partially dependent on murine TLR4.
2008 Volume 83, Issue 6, Page(s) 1336–1344
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Animals ; Chemokine CCL2/genetics ; Chemokine CCL5/genetics ; Chemokine CXCL2/genetics ; Cholesterol, Dietary/administration & dosage ; Cholic Acid/administration & dosage ; Diet, Atherogenic ; Dietary Fats/administration & dosage ; Fatty Liver/etiology ; Hepatitis/etiology ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Messenger/analysis ; Toll-Like Receptor 2/physiology ; Toll-Like Receptor 4/physiology |
| Chemical Substances | Ccl2 protein, mouse ; Ccl5 protein, mouse ; Chemokine CCL2 ; Chemokine CCL5 ; Chemokine CXCL2 ; Cholesterol, Dietary ; Cxcl2 protein, mouse ; Dietary Fats ; RNA, Messenger ; Tlr2 protein, mouse ; Tlr4 protein, mouse ; Toll-Like Receptor 2 ; Toll-Like Receptor 4 ; Cholic Acid (G1JO7801AE) |
| Language | English |
| Publishing date | 2008-06 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. |
| ZDB-ID | 605722-6 |
| ISSN | 1938-3673 ; 0741-5400 |
| ISSN (online) | 1938-3673 |
| ISSN | 0741-5400 |
| DOI | 10.1189/jlb.0607390 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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