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pubmed-article:12960176pubmed:abstractTextMacrophages are pivotal effector cells in the innate immune system. When microbial products bind to pathogen recognition receptors, macrophages are activated and release a broad array of mediators, such as cytokines, that orchestrate the inflammatory responses of the host. Phosphatidic acid (PA) has been implicated as an important metabolite of phospholipid biosynthesis and in membrane remodeling and has been further suggested to be a crucial second messenger in various cellular signaling events. Here we show that PA is an essential regulator of inflammatory response. Deleterious effects of PA are associated with the secretion of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and the production of nitric oxide, prostaglandin E2, which are predominantly released by macrophage Raw264.7 cells. Furthermore, the administration of PA to mice increased the serum cytokine level. Moreover, direct or lipopolysaccharide-induced PA accumulation by macrophages led to the Akt-dependent activation of the mammalian target of rapamycin-p70 S6 kinase 1, a process required for the induction of inflammatory mediators. These findings demonstrate the importance of the role of PA in systemic inflammatory responses, and provide a potential usefulness as specific targets for the development of therapies.lld:pubmed
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pubmed-article:12960176pubmed:authorpubmed-author:RyuSung HoSHlld:pubmed
pubmed-article:12960176pubmed:authorpubmed-author:KimJae-RyongJ...lld:pubmed
pubmed-article:12960176pubmed:authorpubmed-author:BaekSuk-HwanS...lld:pubmed
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pubmed-article:12960176pubmed:authorpubmed-author:KimJung-HyeJHlld:pubmed
pubmed-article:12960176pubmed:authorpubmed-author:KimSeong-Yong...lld:pubmed
pubmed-article:12960176pubmed:authorpubmed-author:ChoiYoung-AeY...lld:pubmed
pubmed-article:12960176pubmed:authorpubmed-author:LimHyung-KyuH...lld:pubmed
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pubmed-article:12960176pubmed:dateRevised2010-11-18lld:pubmed
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pubmed-article:12960176pubmed:articleTitlePhosphatidic acid regulates systemic inflammatory responses by modulating the Akt-mammalian target of rapamycin-p70 S6 kinase 1 pathway.lld:pubmed
pubmed-article:12960176pubmed:affiliationDepartment of Biochemistry & Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.lld:pubmed
pubmed-article:12960176pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:12960176pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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