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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)

Author
item Lee, Joo
item Ye, Jianping
item Gao, Zhanguo
item Youn, Hyung
item Lee, Won
item Zhao, Ling
item Sizemore, Nywana
item Hwang, Daniel

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/1/2003
Publication Date: 7/15/2003
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: 8/24/2016
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