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

277 Citations (Scopus)

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

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Fatty Acids
Toll-Like Receptor 4
Macrophages
Chemical activation
Impurities
Gene expression
Laurates
Gene Expression
Phosphorylation
Palmitic Acid
Docosahexaenoic Acids
JNK Mitogen-Activated Protein Kinases
Mitogens
Cell culture
Monocytes
Suspensions
Cell Culture Techniques
Sodium
Experiments

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Huang, S., Rutkowsky, J. M., Snodgrass, R. G., Ono-Moore, K. D., Schneider, D. A., Newman, J. W., ... 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

Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. / Huang, Shurong; Rutkowsky, Jennifer M.; Snodgrass, Ryan G.; Ono-Moore, Kikumi D.; Schneider, Dina A.; Newman, John W.; Adams, Sean H.; Hwang, Daniel H.

In: Journal of Lipid Research, Vol. 53, No. 9, 09.2012, p. 2002-2013.

Research output: Contribution to journalArticle

Huang, S, Rutkowsky, JM, Snodgrass, RG, Ono-Moore, KD, Schneider, DA, Newman, JW, Adams, SH & Hwang, DH 2012, 'Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways', Journal of Lipid Research, vol. 53, no. 9, pp. 2002-2013. https://doi.org/10.1194/jlr.D029546
Huang S, Rutkowsky JM, Snodgrass RG, Ono-Moore KD, Schneider DA, Newman JW et al. Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. Journal of Lipid Research. 2012 Sep;53(9):2002-2013. https://doi.org/10.1194/jlr.D029546
Huang, Shurong ; Rutkowsky, Jennifer M. ; Snodgrass, Ryan G. ; Ono-Moore, Kikumi D. ; Schneider, Dina A. ; Newman, John W. ; Adams, Sean H. ; Hwang, Daniel H. / Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. In: Journal of Lipid Research. 2012 ; Vol. 53, No. 9. pp. 2002-2013.
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