Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment.
نویسندگان
چکیده
Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0-3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a biological active inflammatory resolution program, regulated by proresolving lipid mediators during postexercise recovery.
منابع مشابه
CALL FOR PAPERS Integrative and Translational Physiology: Inflammation, Immunity, and Organ System Physiology Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment
James F. Markworth, Luke Vella, Benjamin S. Lingard, Dedreia L. Tull, Thusitha W. Rupasinghe, Andrew J. Sinclair, Krishna Rao Maddipati, and David Cameron-Smith School of Exercise and Nutrition Science, Deakin University, Melbourne, Victoria, Australia; Liggins Institute, The University of Auckland, Auckland, New Zealand; Metabolomics Australia, Bio21 Institute for Molecular Science and Biotech...
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عنوان ژورنال:
- American journal of physiology. Regulatory, integrative and comparative physiology
دوره 305 11 شماره
صفحات -
تاریخ انتشار 2013