Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways[S]
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 rep...
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doaj-c8134a3dc6134548b026ee338ffc615d2021-04-28T06:05:23ZengElsevierJournal of Lipid Research0022-22752012-09-0153920022013Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways[S]Shurong Huang0Jennifer M. Rutkowsky1Ryan G. Snodgrass2Kikumi D. Ono-Moore3Dina A. Schneider4John W. Newman5Sean H. Adams6Daniel H. Hwang7Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Department of Anatomy, Physiology and Cell Biology, andWestern Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Department of NutritionWestern Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, University of California , Davis, CAWestern Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, University of California , Davis, CAWestern Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Department of Anatomy, Physiology and Cell Biology, andWestern Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Department of Anatomy, Physiology and Cell Biology, and; Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, University of California , Davis, CAWestern Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Department of Anatomy, Physiology and Cell Biology, and; Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, University of California , Davis, CATo whom correspondence should be addressed. e-mail: daniel.hwang@ars.usda.gov.; Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Department of Anatomy, Physiology and Cell Biology, and; Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, University of California , Davis, CA; To whom correspondence should be addressed. e-mail: daniel.hwang@ars.usda.gov.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-activated-kinase (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.http://www.sciencedirect.com/science/article/pii/S0022227520418437docosahexaenoic acidToll-like receptorsreactive oxygen species |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shurong Huang Jennifer M. Rutkowsky Ryan G. Snodgrass Kikumi D. Ono-Moore Dina A. Schneider John W. Newman Sean H. Adams Daniel H. Hwang |
spellingShingle |
Shurong Huang Jennifer M. Rutkowsky Ryan G. Snodgrass Kikumi D. Ono-Moore Dina A. Schneider John W. Newman Sean H. Adams Daniel H. Hwang Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways[S] Journal of Lipid Research docosahexaenoic acid Toll-like receptors reactive oxygen species |
author_facet |
Shurong Huang Jennifer M. Rutkowsky Ryan G. Snodgrass Kikumi D. Ono-Moore Dina A. Schneider John W. Newman Sean H. Adams Daniel H. Hwang |
author_sort |
Shurong Huang |
title |
Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways[S] |
title_short |
Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways[S] |
title_full |
Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways[S] |
title_fullStr |
Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways[S] |
title_full_unstemmed |
Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways[S] |
title_sort |
saturated fatty acids activate tlr-mediated proinflammatory signaling pathways[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2012-09-01 |
description |
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-activated-kinase (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. |
topic |
docosahexaenoic acid Toll-like receptors reactive oxygen species |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520418437 |
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