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United States Department of Agriculture

Agricultural Research Service

Title: Saturated Fatty Acid Activates But Polyunsaturated Fatty Acid Inhibits Toll-Like Receptor 2 Dimerized with Toll-Like Receptor 6 Or 1

Authors
item Lee, Joo - UNIV OF CALIF DAVIS
item Zhao, Ling - UNIV OF CALIF DAVIS
item Young, Hyung - UNIV OF CALIF DAVIS
item Weatherill, Amy
item Tapping, Richard - UNIV OF ILLINOIS
item Feng, Lili - BAYLOR COLLEGE OF MEDICIN
item Lee, Won - UNIV OF CALIF DAVIS
item Fitzgerald, Katherine - UNIV OF MASSACHUSETTS
item Hwang, Daniel

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 11, 2004
Publication Date: February 11, 2004
Citation: Lee, J.Y., Zhao, L., Young, H., Weatherill, A., Tapping, R., Feng, L., Lee, W.H., Fitzgerald, K., Hwang, D.H. Saturated fatty acid activates but polyunsaturated fatty acid inhibits toll-like receptor 2 dimerized with toll-like receptor 6 or 1. Journal of Biological Chemistry 279(17) 16971-16979, 2004.

Interpretive Summary: We found that dimerization of Toll-like receptors was not affected by fatty acids. Additionally, we found that lauric acid is able to activate toll-like receptors that require acylated fatty acids, whereas docosahexaenoic acid is able to inhibit the activation of all toll-like receptors tested.

Technical Abstract: Toll-like receptor 4 (TLR4) and TLR2 agonists from bacterial origin require acylated saturated fatty acids in their molecules. Previously, we reported that TLR4 activation is reciprocally modulated by saturated and polyunsaturated fatty acids in macrophages. However, it is not known whether fatty acids can modulate the activation of TLR2 or other TLRs for which respective ligands do not require acylated fatty acids. A saturated fatty acid, lauric acid, induced NF B activation when TLR2 was co-transfected with TLR1 or TLR6 in 293T cells, but not when TLR1, 2, 3, 5, 6 or 9 was transfected individually. Docosahexaenoic acid (DHA) suppressed NF B activation and COX-2 expression induced by agonists for TLR2, 3, 4, 5, or 9. Since dimerization is considered as one of the important initial steps for the activation of TLR2 and TLR4, we determined whether the fatty acids modulate the dimerization. However, neither lauric acid nor DHA affected heterodimerization of TLR2 with TLR6 as well as homodimerization of TLR4 as determined by co-immunoprecipitation assays suggesting that the dimerization is not the mechanism by which fatty acids modulate the activation of TLRs. Together, these results demonstrate that lauric acid activates TLR2 dimers as well as TLR4 for which respective bacterial agonists require acylated fatty acids whereas DHA inhibits the activation of all TLRs tested. Thus, responsiveness of different cell types and tissues to saturated fatty acids would depend on the expression of TLR4 or TLR2 with either TLR1 or TLR6 that can dimerize. These results also suggest a possibility that inflammatory responses induced by activation of TLRs can be differentially modulated by types of dietary fatty acids.

Last Modified: 10/24/2014