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United States Department of Agriculture

Agricultural Research Service

Title: Reciprocal Modulation of Toll-Like Receptor-4 Signaling Pathways Involving Myd88 and Phosphatidylinositol 3-Kinase/akt by Saturated and Polyunsaturated Fatty Acids

Authors
item Lee, Joo - UNIV OF CALIF DAVIS
item Ye, Jianping - PENNINGTON BIOMEDICAL
item Gao, Zhanguo - PENNINGTON BIOMEDICAL
item Youn, Hyung - UNIV OF CALIF DAVIS
item Lee, Won - UNIV OF CALIF DAVIS
item Zhao, Ling - UNIV OF CALIF DAVIS
item Sizemore, Nywana - CLEVELAND CLINIC FND
item HWANG, DANIEL

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 1, 2003
Publication Date: July 15, 2003
Citation: Lee, J., Ye, J., Gao, Z., Youn, H., Lee, W., Zhao, L., Sizemore, N., Hwang, D.H. 2003. RECIPROCAL MODULATION OF TOLL-LIKE RECEPTOR-4 SIGNALING PATHWAYS INVOLVING MYD88 AND PHOSPHATIDYLINOSITOL 3-KINASE/AKT BY SATURATED AND POLYUNSATURATED FATTY ACIDS. Journal of Biological Chemistry 278 (39) 37041-37051, 2003.

Interpretive Summary: Toll-like receptors (TLRs) play a critical role in inducing innate immune responses in mammals by recognizing conserved athogen-associated molecular patterns (PAMPs) of bacteria. So far, ten human TLRs have been cloned. The TLR agonists include lipopolysaccaride (LPS) for TLR4, peptidoglycan for TLR2 and 6, double-stranded RNA for TLR3, flagellin for TLR5, and imidazoquinolines and unmethylated CpG motifs in bacterial DNA for TLR7 and 9, respectively. TLR4 can be activated by non-bacterial agonists such as heat shock protein 60, fibronectin, taxol, respiratory syncytical virus coat protein and saturated fatty acids.

Technical Abstract: Toll-like receptor 4 (TLR4) can be activated by non-bacterial agonists including saturated fatty acids. However, downstream signaling pathways activated by non-bacterial agonists are not known. Thus, we determined the downstream signaling pathways derived from saturated fatty acid-induced TLR4 activation. The results suggest that saturated and polyunsaturated fatty acids reciprocaly modulate the activation of TLR4 and its downstream signaling pathways involving MyD88/IRAK/TRAF6 and P13K/AKT, and further suggest a possibility that TLR4-mediated target gene expression and cellular responses are also differentially modulated by saturated and unsaturated fatty acids.

Last Modified: 9/10/2014
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