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https://hdl.handle.net/2440/7506
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Type: | Journal article |
Title: | A novel long chain polyunsaturated fatty acid, b-oxa 21:3n-3, inhibits T lymphocyte proliferation, cytokine production, delayed-type hypersensitivity, and carrageenan-induced paw reaction and selectively targets intracellular signals |
Author: | Costabile, M. Hii, C. Robinson, B. Rathjen, D. Pitt, M. Easton, C. Miller, R. Poulos, A. Murray, A. Ferrante, A. |
Citation: | Journal of Immunology, 2001; 167(7):3980-3987 |
Publisher: | Amer Assoc Immunologists |
Issue Date: | 2001 |
ISSN: | 0022-1767 1550-6606 |
Abstract: | A novel polyunsaturated fatty acid (PUFA), beta-oxa 21:3n-3, containing an oxygen atom in the beta position, was chemically synthesized, and found to have more selective biological activity than the n-3 PUFA, docosahexaenoic acid (22:6n-3) on cells of the immune system. Although beta-oxa 21:3n-3 was very poor compared with 22:6n-3 at stimulating oxygen radical production in neutrophils, it was more effective at inhibiting human T lymphocyte proliferation (IC(50) of 1.9 vs 5.2 microM, respectively). beta-Oxa 21:3n-3 also inhibited the production of TNF-beta, IFN-gamma, and IL-2 by purified human T lymphocytes stimulated with PHA plus PMA, anti-CD3 plus anti-CD28 mAbs, or PMA plus A23187. Metabolism of beta-oxa 21:3n-3 via the cyclooxygenase and lipoxygenase pathways was not required for its inhibitory effects. Consistent with its ability to suppress T lymphocyte function, beta-oxa 21:3n-3 significantly inhibited the delayed-type hypersensitivity response and carrageenan-induced paw edema in mice. In T lymphocytes, beta-oxa 21:3n-3 inhibited the agonist-stimulated translocation of protein kinase C-betaI and -epsilon, but not -alpha, -betaII, or -theta to a particulate fraction, and also inhibited the activation of the extracellular signal-regulated protein kinase, but not c-Jun NH(2)-terminal kinase and p38. In contrast, 22:6n-3 had no effects on these protein kinase C isozymes. The increase in antiinflammatory activity and loss of unwanted bioaction through the generation of a novel synthetic 22:6n-3 analogue provides evidence for a novel strategy in the development of anti-inflammatory agents by chemically engineering PUFA. |
Keywords: | Neutrophils T-Lymphocytes Cells, Cultured Cytoplasm Humans Hypersensitivity, Delayed Edema Mitogen-Activated Protein Kinases Protein Kinase C Carrageenan Docosahexaenoic Acids Fatty Acids, Unsaturated Anti-Inflammatory Agents Cytokines Enzyme Inhibitors Lymphocyte Activation Signal Transduction Respiratory Burst Dose-Response Relationship, Drug |
DOI: | 10.4049/jimmunol.167.7.3980 |
Published version: | http://dx.doi.org/10.4049/jimmunol.167.7.3980 |
Appears in Collections: | Aurora harvest Paediatrics publications |
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