Differential modulation of Toll-like receptors by fatty acids: Preferential inhibition by n-3 polyunsaturated fatty acids

Joo Y. Lee, Anthony Plakidas, Won H. Lee, Anne Heikkinen, Prithiva Chanmugam, George Bray, Daniel H. Hwang

Research output: Contribution to journalArticlepeer-review

434 Scopus citations


Human subjects consuming fish oil showed a significant suppression of cyclooxygenase-2 (COX-2) expression in blood monocytes when stimulated in vitro with lipopolysaccharide (LPS), an agonist for Toll-like receptor 4 (TLR4). Results with a murine monocytic cell line (RAW 264.7) stably transfected with COX-2 promoter reporter gene also demonstrated that LPS-induced COX-2 expression was preferentially inhibited by docosahexaenoic acid (DHA, C22:6n-3) and eicosapentaenoic acid (EPA, C20:5n-3), the major n-3 polyunsaturated fatty acids (PUFAs) present in fish oil. Additionally, DHA and EPA significantly suppressed COX-2 expression induced by a synthetic lipopeptide, a TLR2 agonist. These results correlated with the preferential suppression of LPS- or lipopeptide-induced NFκB activation by DHA and EPA. The target of inhibition by DHA is TLR itself or its associated molecules, but not downstream signaling components. In contrast, COX-2 expression by TLR2 or TRL4 agonist was potentiated by lauric acid, a saturated fatty acid. These results demonstrate that inhibition of COX-2 expression by n-3 PUFAs is mediated through the modulation of TLR-mediated signaling pathways. Thus, the beneficial or detrimental effects of different types of dietary fatty acids on the risk of the development of many chonic inflammatory diseases may be in part mediated through the modulation of TLRs.

Original languageEnglish (US)
Pages (from-to)479-486
Number of pages8
JournalJournal of Lipid Research
Issue number3
StatePublished - Mar 2003
Externally publishedYes


  • Cyclooxygenase-2
  • n-3 polyunsaturated fatty acids
  • NFκB
  • Toll-like receptors
  • Unsaturated and saturated fatty acids

ASJC Scopus subject areas

  • Endocrinology


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