期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 59, 期 5, 页码 729-741出版社
BIRKHAUSER VERLAG AG
DOI: 10.1007/s00018-002-8462-2
关键词
eicosanoids; lipid mediators; signal transduction; aspirin; inflammation; leukocytes
资金
- NHLBI NIH HHS [NHLBI-HL-56383, NHLBI-K08-HL03788, R01 HL068669] Funding Source: Medline
- NIDDK NIH HHS [DK-50305] Funding Source: Medline
- NIGMS NIH HHS [GM-38765] Funding Source: Medline
Lipoxins (LX) and aspirin-triggered 15-epimer LX are leukocyte-derived eicosanoids generated during host defense that serve as down-regulatory signals. The specific intracellular events that govern cellular responses to inhibitory extracellular signals are of wide interest in order to understand pivotal intracellular events in diseases characterized by enhanced inflammatory responses, such as asthma, rheumatoid arthritis and atherosclerosis. We recently uncovered a novel role for polyisoprenyl phosphates, in particular presqualene diphosphate (PSDP), as natural down-regulatory signals in human neutrophils that directly inhibit phospholipase D and superoxide anion generation. Activation of LXA(4) receptors (ALXR) reverses proinflammatory receptor-initiated decrements in PSDP and inhibits cellular responses. These findings represent evidence for a novel paradigm for lipid-protein interactions in the control of cellular responses, namely receptor-initiated degradation of repressor lipids that is subject to regulation by aspirin treatment via the actions of aspirin-triggered 15-epimer LX at the ALXR, and identify new templates for antiinflammatory drugs by design.
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