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https://hdl.handle.net/2440/17339
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Type: | Journal article |
Title: | Cutting edge: Novel role of lipoxygenases in the inflammatory response: Promotion of TNF mRNA decay by 15-hydroperoxyeicosatetraenoic acid in a monocytic cell line |
Author: | Ferrante, J. Ferrante, A. |
Citation: | Journal of Immunology, 2005; 174(6):3169-3172 |
Publisher: | American Association of Immunologists |
Issue Date: | 2005 |
ISSN: | 0022-1767 1550-6606 |
Statement of Responsibility: | Judith V. Ferrante and Antonio Ferrante |
Abstract: | The metabolism of arachidonic acid via the lipoxygenase and cyclooxygenase pathways generates metabolites that regulate the inflammatory response. Although products of lipoxygenase are classically proinflammatory, recently it has been demonstrated that lipoxins, 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and 15-hydroxyeicosatetraenoic acid exhibit anti-inflammatory activity. We now demonstrate for the first time that 15-HPETE regulates the production of the proinflammatory cytokine TNF posttranscriptionally by promoting degradation of LPS-induced TNFmRNA in a human monocytic cell line, Mono Mac 6. 15-HPETE causes a significant increase in the rate of TNF but not G3PDHmRNA degradation in the presence of the transcription inhibitor, actinomycin D. The decay of TNFmRNA is accelerated 1.7-fold, and its half-life is decreased by 57%. In view of its chemical and physical properties, we propose that 15-HPETE may function by destabilizing TNFmRNA by interaction with a trans-activating protein bound to the AU-rich element of TNFmRNA. |
Keywords: | Monocytes Cell Line Humans Inflammation Lipid Peroxides Lipoxygenase Arachidonic Acid Leukotrienes Tumor Necrosis Factor-alpha RNA, Messenger RNA Stability |
Rights: | Copyright © 2005 by The American Association of Immunologists, Inc. |
DOI: | 10.4049/jimmunol.174.6.3169 |
Published version: | http://dx.doi.org/10.4049/jimmunol.174.6.3169 |
Appears in Collections: | Aurora harvest 6 Paediatrics publications |
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