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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690
Innate Immunity: The Virtues of a Nonclonal System of Recognition
Medzhitov, R., & Janeway, C. A. (1997) · Cell · doi:10.1016/s0092-8674(00)80412-2 · Cited by 2,434
Lee, J. Y., Sohn, K. H., Rhee, S. H., & Hwang, D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011695200 · Cited by 1,299
Self-citationNguyen, M. T. A., Favelyukis, S., Nguyen, A.-K., Reichart, D., Scott, P. A., Jenn, A., Liu-Bryan, R., Glass, C. K., Neels, J. G., & Olefsky, J. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706762200 · Cited by 1,035
Michelsen, K. S., Wong, M. H., Shah, P. K., Zhang, W., Yano, J., Doherty, T. M., Akira, S., Rajavashisth, T. B., & Arditi, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403249101 · Cited by 1,019
Park, H. S., Jung, H. Y., Park, E. Y., Kim, J., Lee, W. J., & Bae, Y. S. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3589 · Cited by 635
Lee, J. Y., Ye, J., Gao, Z., Youn, H. S., Lee, W. H., Zhao, L., Sizemore, N., & Hwang, D. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305213200 · Cited by 524
Self-citationTlr-4 deficiency selectively protects against obesity induced by diets high in saturated fat
Davis, J. E., Gabler, N. K., Walker‐Daniels, J., & Spurlock, M. E. (2008) · Obesity · doi:10.1038/oby.2008.210 · Cited by 334
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
Cardioprotective mechanism of omega-3 polyunsaturated fatty acids
Endo, J., & Arita, M. (2016) · Journal of Cardiology · doi:10.1016/j.jjcc.2015.08.002 · Cited by 369
n -3 Fatty acids, inflammation and immunity: new mechanisms to explain old actions
Calder, P. C. (2013) · Proceedings of the Nutrition Society · doi:10.1017/s0029665113001031 · Cited by 364
Inflammation and the Metabolic Syndrome: The Tissue-Specific Functions of NF-κB
Catrysse, L., & van Loo, G. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.01.006 · Cited by 329
Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity
Donath, M. Y., Dalmas, É., Sauter, N. S., & Böni-Schnetzler, M. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.05.001 · Cited by 338
Zhu, X., Owen, J. S., Wilson, M. D., Li, H., Griffiths, G. L., Thomas, M. J., Hiltbold, E. M., Fessler, M. B., & Parks, J. S. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m006486 · Cited by 331
The Influence of Dietary Fatty Acids on Immune Responses
Radzikowska, U., Rinaldi, A. O., Çelebi Sözener, Z., Karaguzel, D., Wojcik, M., Cypryk, K., Akdis, M., Akdis, C. A., & Sokolowska, M. (2019) · Nutrients · doi:10.3390/nu11122990 · Cited by 306
Zhang, J., Zhang, Q., Lou, Y., Fu, Q., Chen, Q., Wei, T., Yang, J., Tang, J., Wang, J., Chen, Y., et al. (2018) · Hepatology · doi:10.1002/hep.29681 · Cited by 286
Snodgrass, R. G., Huang, S., Choi, I.-W., Rutledge, J. C., & Hwang, D. H. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300298 · Cited by 243
Self-citationSaturated fatty acids activate microglia via Toll-like receptor 4/NF-κB signalling
Wang, Z., Liu, D., Wang, F., Liu, S., Zhao, S., Ling, E.-A., & Hao, A. (2012) · British Journal of Nutrition · doi:10.1017/s0007114511002868 · Cited by 239
Long-chain fatty acids and inflammation
Calder, P. C. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s0029665112000067 · Cited by 222
Toll-Like Receptors: Regulators of the Immune Response in the Human Gut
Hug, H., Mohajeri, M., & La Fata, G. (2018) · Nutrients · doi:10.3390/nu10020203 · Cited by 217
PM2.5 Exposure and Asthma Development: The Key Role of Oxidative Stress
Liu, K., Hua, S., & Song, L. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/3618806 · Cited by 187
Shaikh, S. R., Kinnun, J. J., Leng, X., Williams, J. A., & Wassall, S. R. (2015) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2014.04.020 · Cited by 179
Haslund‐Vinding, J., McBean, G., Jaquet, V, & Vilhardt, F. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13425 · Cited by 169
Shaikh, S. R. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2011.07.001 · Cited by 134
Lipolysis of triglyceride-rich lipoproteins, vascular inflammation, and atherosclerosis
Schwartz, E. A., & Reaven, P. D. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.09.021 · Cited by 130
Nitroxidative signaling mechanisms in pathological pain
Grace, P. M., Gaudet, A. D., Staikopoulos, V., Maier, S. F., Hutchinson, M. R., Salvemini, D., & Watkins, L. R. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.10.003 · Cited by 128
Foucault, A., Mathé, V., Lafont, R., Even, P., Dioh, W., Veillet, S., Tomé, D., Huneau, J., Hermier, D., & Quignard‐Boulangé, A. (2012) · Obesity · doi:10.1038/oby.2011.257 · Cited by 122
Villacorta, L., Chang, L., Salvatore, S. R., Ichikawa, T., Zhang, J., Petrovic-Djergovic, D., Jia, L., Carlsen, H., Schopfer, F. J., Freeman, B. A., et al. (2013) · Cardiovascular Research · doi:10.1093/cvr/cvt002 · Cited by 116
Lipid rafts in glial cells: role in neuroinflammation and pain processing
Miller, Y. I., Navia-Pelaez, J. M., Corr, M., & Yaksh, T. L. (2020) · Journal of Lipid Research · doi:10.1194/jlr.tr119000468 · Cited by 112
Mechanisms of Lipotoxicity in the Cardiovascular System
Wende, A. R., Symons, J. D., & Abel, E. D. (2012) · Current Hypertension Reports · doi:10.1007/s11906-012-0307-2 · Cited by 110
The vascular contribution to Alzheimer's disease
Altman, R., & Rutledge, J. C. (2010) · Clinical Science · doi:10.1042/cs20100094 · Cited by 93
Brown, D. G., Soto, R., Yandamuri, S., Stone, C., Dickey, L., Gomes-Neto, J. C., Pastuzyn, E. D., Bell, R., Petersen, C., Buhrke, K., et al. (2019) · eLife · doi:10.7554/elife.47117 · Cited by 60
Nishimura, Y., Moriyama, M., Kawabe, K., Satoh, H., Takano, K., Azuma, Y.-T., & Nakamura, Y. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2587-7 · Cited by 56
What is the best diet for cardiovascular wellness? A comparison of different nutritional models
Migliaccio, S., Brasacchio, C., Pivari, F., Salzano, C., Barrea, L., Muscogiuri, G., Savastano, S., Colao, A., & on behalf of Obesity Programs of nutrition, E. (2020) · International Journal of Obesity Supplements · doi:10.1038/s41367-020-0018-0 · Cited by 39
Vijay-Kumar, M., Vanegas, S. M., Patel, N., Aitken, J. D., Ziegler, T. R., & Ganji, V. (2011) · Nutrition & Metabolism · doi:10.1186/1743-7075-8-16 · Cited by 29
“In contrast, DHA of FO inhibits the dimerization and recruitment of TLR-4 into the membrane [40] leading to attenuated TLR-4 signaling.”
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
