The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Fatty Acids Modulate Toll-like Receptor 4 Activation through Regulation of Receptor Dimerization and Recruitment into Lipid Rafts in a Reactive Oxygen Species-dependent Manner
Open accessAbstract
The saturated fatty acids acylated on Lipid A of lipopolysaccharide (LPS) or bacterial lipoproteins play critical roles in ligand recognition and receptor activation for Toll-like Receptor 4 (TLR4) and TLR2. The results from our previous studies demonstrated that saturated and polyunsaturated fatty acids reciprocally modulate the activation of TLR4. However, the underlying mechanism has not been understood. Here, we report for the first time that the saturated fatty acid lauric acid induced dimerization and recruitment of TLR4 into lipid rafts, however, dimerization was not observed in non-lipid raft fractions. Similarly, LPS and lauric acid enhanced the association of TLR4 with MD-2 and downstream adaptor molecules, TRIF and MyD88, into lipid rafts leading to the activation of downstream signaling pathways and target gene expression. However, docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, inhibited LPS- or lauric acid-induced dimerization and recruitment of TLR4 into lipid raft fractions. Together, these results demonstrate that lauric acid and DHA reciprocally modulate TLR4 activation by regulation of the dimerization and recruitment of TLR4 into lipid rafts. In addition, we showed that TLR4 recruitment to lipid rafts and dimerization were coupled events mediated at least in part by NADPH oxidase-dependent reactive oxygen species generation. These results provide a new insight in understanding the mechanism by which fatty acids differentially modulate TLR4-mediated signaling pathway and consequent inflammatory responses which are implicated in the development and progression of many chronic diseases.
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Cites
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TLR4 links innate immunity and fatty acid-induced insulin resistance
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Cited by
Omega-3 Fatty Acids and Cardiovascular Disease
Mozaffarian, D., & Wu, J. H. Y. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.06.063 · Cited by 1,771
Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance
Calder, P. C. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.08.010 · Cited by 1,717
Omega-3 fatty acids and inflammatory processes: from molecules to man
Calder, P. C. (2017) · Biochemical Society Transactions · doi:10.1042/bst20160474 · Cited by 1,456
Holland, W. L., Bikman, B. T., Wang, L.-P., Yuguang, G., Sargent, K. M., Bulchand, S., Knotts, T. A., Shui, G., Clegg, D. J., Wenk, M. R., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43378 · Cited by 705
Saturated fatty acids trigger TLR4-mediated inflammatory response
Rocha, D. M., Caldas, A. P., Oliveira, L. L., Bressan, J., & Hermsdorff, H. H. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.11.015 · Cited by 492
Metadata
- Authors
- Wong, S. W., Kwon, M.-J., Choi, A. M. K., Kim, H.-P., Nakahira, K., & Hwang, D. H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 284
- Issue
- 40
- Pages
- 27384-27392
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2064399682
- Cited by
- 562
- References
- 9
- FWCI
- 12.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Fatty Acids Modulate Toll-like Receptor 4 Activation through Regulation of Receptor Dimerization and Recruitment into Lipid Rafts in a Reactive Oxygen Species-dependent Manner. https://app.cochat.ai/papers/10.1074/jbc.m109.044065
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- Wong, S. W., Kwon, M.-J., Choi, A. M. K., Kim, H.-P., Nakahira, K., & Hwang, D. H. (2009). Fatty Acids Modulate Toll-like Receptor 4 Activation through Regulation of Receptor Dimerization and Recruitment into Lipid Rafts in a Reactive Oxygen Species-dependent Manner. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m109.044065
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