Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways

Shurong Huang, Jennifer M. Rutkowsky, Ryan G. Snodgrass, Kikumi D. Ono-Moore, Dina A. Schneider, John W. Newman, Sean H. Adams, Daniel H. Hwang

Research output: Contribution to journalArticle

301 Scopus citations

Abstract

Toll-like receptor 4 (TLR4) and TLR2 were shown to be activated by saturated fatty acids (SFAs) but inhibited by docosahexaenoic acid (DHA). However, one report suggested that SFA-induced TLR activation in cell culture systems is due to contaminants in BSA used for solubilizing fatty acids. This report raised doubt about proinflammatory effects of SFAs. Our studies herein demonstrate that sodium palmitate (C16:0) or laurate (C12:0) without BSA solubilization induced phosphorylation of inhibitor of nuclear factor -κB α, c-Jun N-terminal kinase (JNK), p44/42 mitogen-activatedkinase (ERK), and nuclear factor-κB subunit p65, and TLR target gene expression in THP1 monocytes or RAW264.7 macrophages, respectively, when cultured in low FBS (0.25%) medium. C12:0 induced NFκB activation through TLR2 dimerized with TLR1 or TLR6, and through TLR4. Because BSA was not used in these experiments, contaminants in BSA have no relevance. Unlike in suspension cells (THP-1), BSA-solubilized C16:0 instead of sodium C16:0 is required to induce TLR target gene expression in adherent cells (RAW264.7). C16:0-BSA transactivated TLR2 dimerized with TLR1 or TLR6 and through TLR4 as seen with C12:0. These results and additional studies with the LPS sequester polymixin B and in MyD88 -/- macrophages indicated that SFA-induced activation of TLR2 or TLR4 is a fatty acid-specific effect, but not due to contaminants in BSA or fatty acid preparations.

Original languageEnglish (US)
Pages (from-to)2002-2013
Number of pages12
JournalJournal of Lipid Research
Volume53
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • Docosahexaenoic acid
  • Reactive oxygen species
  • Toll-like receptors

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

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  • Cite this

    Huang, S., Rutkowsky, J. M., Snodgrass, R. G., Ono-Moore, K. D., Schneider, D. A., Newman, J. W., Adams, S. H., & Hwang, D. H. (2012). Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. Journal of Lipid Research, 53(9), 2002-2013. https://doi.org/10.1194/jlr.D029546