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Modulation of Inflammatory Cytokines by Omega-3 Fatty Acids

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Book cover Lipids in Health and Disease

Part of the book series: Subcellular Biochemistry ((SCBI,volume 49))

Abstract

Many human diseases have been linked to inflammation, which is mediated by a number of chemical molecules including lipid mediators and cytokines. Polyunsaturated fatty acids (omega-6 and omega-3 fatty acids) are the precursors of the lipid mediators and play an important role in regulation of inflammation. Generally, omega-6 fatty acids (e.g. arachidonic acid) promote inflammation whereas omega-3 fatty acids (e.g. eicosapentaenoic acid and docosahexaenoic acid) have anti-inflammatory properties. Omega-3 fatty acids dampen inflammation through multiple pathways. On the one hand, omega-3 fatty acids inhibit the formation of omega-6 fatty acids-derived pro-inflammatory eicosanoids (e.g. PGE2 and LTB4), and on the other hand these fatty acids can form several potent anti-inflammatory lipid mediators (e.g. resolvins and protectins). These together directly or indirectly suppress the activity of nuclear transcription factors, such as NFκB, and reduce the production of pro-inflammatory enzymes and cytokines, including COX-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. This chapter focuses on the evidence from recent studies using new experimental models.

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References

  • Arita, M., Bianchini, F., Aliberti, J., Sher, A., Chiang, N., Hong, S., Yang, R., Petasis, N. A. and Serhan, C. N. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 201 (2005a) 713–722.

    Article  CAS  Google Scholar 

  • Arita, M., Yoshida, M., Hong, S., Tjonahen, E., Glickman, J. N., Petasis, N. A., Blumberg, R. S. and Serhan, C. N. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci USA 102 (2005b) 7671–7676.

    Article  CAS  Google Scholar 

  • Babcock, T. A., Helton, W. S., Hong, D. and Espat, N. J. Omega-3 fatty acid lipid emulsion reduces LPS-stimulated macrophage TNF-alpha production. Surg Infect (Larchmt) 3 (2002): 145–149.

    Article  Google Scholar 

  • Bhattacharya, A., Chandrasekar, B., Rahman, M. M., Banu, J., Kang, J. X. and Fernandes, G.. Inhibition of inflammatory response in transgenic fat-1 mice on a calorie-restricted diet. Biochem Biophys Res Commun 349 (2006) 925–930.

    Article  PubMed  CAS  Google Scholar 

  • Blok, W.L., Katan, M.B., and van der Meer, J.W.M. Modulation of inflammation and cytokine production by dietary n-3 fatty acids. J Nutr 126 (1996) 1515–1533.

    PubMed  CAS  Google Scholar 

  • Calder P.C. n–3 Polyunsaturated fatty acids, inflammation, and inflammatory disease. Am J Clin Nutr. 83 (2006)1505S–1519S.

    PubMed  CAS  Google Scholar 

  • Calder, P.C. Immunomodulation by omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids 77 (2007) 327–335.

    Article  PubMed  CAS  Google Scholar 

  • Collart, M.A., Baeuerle, P. and Vassalli, P. Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. Mol Cell Biol 10 (1990) 1498–1506.

    PubMed  CAS  Google Scholar 

  • Connor, K.M., SanGiovanni, J.P., Lofqvist, C., Aderman, C.M., Chen, J., Higuchi, A., Hong, S., Pravda, E.A., Majchrzak, S., Carper, D., Hellstrom, A., Kang, J.X., Chew, E.Y., Salem, N., Jr., Serhan, C.N. and Smith, L.E. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med 13 (2007) 868–873.

    Article  PubMed  CAS  Google Scholar 

  • Dinarello, C. A. Proinflammatory cytokines. Chest 118 (2000) 503–508.

    Article  PubMed  CAS  Google Scholar 

  • Endres, S., Ghorbani, R., Kelley, V. E., Georgilis, K., Lonnemann, G., van der Meer, J.W., Cannon, J.G., Rogers, T. S., Klempner, M.S., Weber, P.C. and et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 320 (1989) 265–271.

    PubMed  CAS  Google Scholar 

  • Hayden, M. S. and Ghosh, S. Shared principles in NF-kappaB signaling. Cell 132 (2008) 344–362.

    Article  PubMed  CAS  Google Scholar 

  • Hayden, M. S., West, A. P. and Ghosh, S. NF-kappaB and the immune response. Oncogene 25 (2006) 6758–6780.

    Article  PubMed  CAS  Google Scholar 

  • Hiscott, J., Marois, J., Garoufalis, J., D'Addario, M., Roulston, A., Kwan, I., Pepin, N., Lacoste, J., Nguyen, H., Bensi, G. and et al. Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Mol Cell Biol 13 (1993) 6231–6240.

    PubMed  CAS  Google Scholar 

  • Hong, S., Gronert, K., Devchand, P. R., Moussignac, R. L. and Serhan, C. N. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 278 (2003) 14677–14687.

    Article  PubMed  CAS  Google Scholar 

  • Hudert, C. A., Weylandt, K. H., Lu, Y., Wang, J., Hong, S., Dignass, A., Serhan, C. N. and Kang, J. X. Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis. Proc Natl Acad Sci USA 103 (2006) 11276–11281.

    Article  PubMed  CAS  Google Scholar 

  • James, M. J., Gibson, R. A. and Cleland, L. G. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr 71 (2000) 343S–348S.

    PubMed  CAS  Google Scholar 

  • Kang, J.X. Fat-1 transgenic mice: a new model for omega-3 research. Prostaglandins Leukot Essent Fatty Acids 77 (2007) 263–267.

    Article  PubMed  CAS  Google Scholar 

  • Kang J.X., Wang, J., Wu, L., Kang, Z.B. Fat-1 transgenic mice convert n-6 to n-3 fatty acids. Nature 427 (2004) 504.

    Article  PubMed  CAS  Google Scholar 

  • Li, Y., Kang, J.K., and Leaf, A. Differential effects of various eicosanoids on the production or prevention of arrhythmias in cultured neonatal rat cardiac myocytes. Prostaglandins 54 (1997) 511–530.

    Article  PubMed  CAS  Google Scholar 

  • Libby, P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev 65 (2007) S140–S146.

    Article  PubMed  Google Scholar 

  • Martin, M. U. and Wesche, H. Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochim Biophys Acta 1592 (2002) 265–280.

    Article  PubMed  CAS  Google Scholar 

  • Mayer, J., Rau, B., Gansauge, F. and Beger, H. G. Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications. Gut 47 (2000) 546–552.

    Article  PubMed  CAS  Google Scholar 

  • Novak, T. E., Babcock, T. A., Jho, D. H., Helton, W. S. and Espat, N. J. NF-kappa B inhibition by omega -3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol Lung Cell Mol Physiol 284 (2003) L84–L89.

    PubMed  CAS  Google Scholar 

  • Nowak, J., Weylandt, K. H., Habbel, P., Wang, J., Dignass, A., Glickman, J. N. and Kang, J. X. Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids. Carcinogenesis 28 (2007) 1991–1995.

    Article  PubMed  CAS  Google Scholar 

  • Papadakis, K. A. and Targan, S. R. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med 51 (2000) 289–298.

    Article  PubMed  CAS  Google Scholar 

  • Peters-Golden, M., Canetti, C., Mancuso, P. and Coffey, M. J. Leukotrienes: underappreciated mediators of innate immune responses. J Immunol 174 (2005) 589–594.

    PubMed  CAS  Google Scholar 

  • Richard, A.G., Thomas, J.K., Barbara, A.O. and Janis, K. (Editors) Immunology (5th Edition, W. H. Freeman and Company, New York) 2000; pp 338–360.

    Google Scholar 

  • Sass, G., Heinlein, S., Agli, A., Bang, R., Schumann, J. and Tiegs, G.. Cytokine expression in three mouse models of experimental hepatitis. Cytokine 19 (2002) 115–120.

    Article  PubMed  CAS  Google Scholar 

  • Schmocker, C., Weylandt, K. H., Kahlke, L., Wang, J., Lobeck, H., Tiegs, G., Berg, T. and Kang, J. X. Omega-3 fatty acids alleviate chemically induced acute hepatitis by suppression of cytokines. Hepatology 45 (2007) 864–869.

    Article  PubMed  CAS  Google Scholar 

  • Schwab, J. M., Chiang, N., Arita, M. and Serhan, C. N.. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447 (2007) 869–74.

    Article  PubMed  CAS  Google Scholar 

  • Sellers, M. M. and Stallone, J. N. Sympathy for the Devil: The Role of Thromboxane in the Regulation of Vascular Tone and Blood Pressure. Am J Physiol Heart Circ Physiol. (2008) (Epub ahead of print-- PMID: 18310512).

    Google Scholar 

  • Serhan, C. N. Yacoubian, S., and Yang, Y. Anti-Inflammatory and Proresolving Lipid Mediators. Annu Rev Pathol. 28 (2008) 279–312.

    Article  Google Scholar 

  • Shapiro, A.C., Wu, D., and Meydani, S.N. Eicosanoids derived from arachidonic and eicosapentaenoic acids inhibit T cell proliferative response. Prostaglandins 45 (1993) 229–240

    Article  PubMed  CAS  Google Scholar 

  • Sijben, J. W. and Calder, P. C. Differential immunomodulation with long-chain n-3 PUFA in health and chronic disease. Proc Nutr Soc 66 (2007) 237–259.

    Article  PubMed  CAS  Google Scholar 

  • Simopoulos, A. P. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 21 (2002) 495–505.

    PubMed  CAS  Google Scholar 

  • Stimac, D., Fisic, E., Milic, S., Bilic-Zulle, L. and Peric, R. Prognostic values of IL-6, IL-8, and IL-10 in acute pancreatitis. J Clin Gastroenterol 40 (2006) 209–212.

    Article  PubMed  CAS  Google Scholar 

  • Tilg, H., Jalan, R., Kaser, A., Davies, N. A., Offner, F. A., Hodges, S. J., Ludwiczek, O., Shawcross, D., Zoller, H., Alisa, A., Mookerjee, R. P., Graziadei, I., Datz, C., Trauner, M., Schuppan, D., Obrist, P., Vogel, W. and Williams, R. Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis. J Hepatol 38 (2003) 419–425.

    Article  PubMed  CAS  Google Scholar 

  • White, K. E., Ding, Q., Moore, B. B., Peters-Golden, M., Ware, L. B., Matthay, M. A. and Olman, M. A. Prostaglandin E2 mediates IL-1beta-related fibroblast mitogenic effects in acute lung injury through differential utilization of prostanoid receptors. J Immunol 180 (2008) 637–646.

    PubMed  CAS  Google Scholar 

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Kang, J.X., Weylandt, K.H. (2008). Modulation of Inflammatory Cytokines by Omega-3 Fatty Acids. In: Quinn, P.J., Wang, X. (eds) Lipids in Health and Disease. Subcellular Biochemistry, vol 49. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8831-5_5

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