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The requirement of PKC‐alpha and NF‐kappa B activation for phosphatidic acid‐induced iNOS expression
Author(s) -
Lee JinGu,
Park DaeWeon,
Lee SunHye,
Lim EunJung,
Kim JaeRyong,
Lee Chuhee,
Baek SukHwan
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a951-a
Subject(s) - phosphatidic acid , microbiology and biotechnology , signal transduction , nfkb1 , nf κb , protein kinase c , inflammation , chemistry , transcription factor , biology , cancer research , immunology , biochemistry , phospholipid , membrane , gene
Host innate immune responses to bacterial infections are primarily mediated by macrophages or monocytes. Stimulation of these cells initiates secretion of pro‐inflammatory mediators, which promote the elimination of infectious agents and the induction of tissue repair. 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. Previously, we reported that PA acts as an important mediator which specifically stimulates pro‐inflammatory cytokines (TNF‐α, IL‐1β, and IL‐6) and mediators (NO and PGE 2 ) synthesis in macrophages. Here we show that PA induced iNOS expression in time and dose‐dependently. PKC‐α activation is required for PA‐induced iNOS expression, which was confirmed by PKC‐α overexpression and PKC‐α siRNA. NF‐κB is an important transcription factor for PA‐induced iNOS expression because inhibition of NF‐κB suppressed those effects. Moreover NF‐κB activation was blocked when PKC‐α was inhibited. Taken together, we suggest that PA induces iNOS expression through PKC‐α and NF‐κB signal pathway. 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. * This work was supported by a grant R13‐2005‐005‐01003‐0 (2005) from the Aging‐Associated Vascular Disease Research Center at Yeungnam University of Korea Science and Engineering Foundation.