Prostaglandin D2Inhibits Inducible Nitric Oxide Synthase Expression in Rat Vascular Smooth Muscle Cells
作者:
Hiroshi Nagoshi,
Yoshio Uehara,
Fumihiko Kanai,
Shin Maeda,
Tsutomu Ogura,
Atsuo Goto,
Teruhiko Toyo‐oka,
Hiroyasu Esumi,
Takao Shimizu,
Masao Omata,
期刊:
Circulation Research
(OVID Available online 1998)
卷期:
Volume 82,
issue 2
页码: 204-209
ISSN:0009-7330
年代: 1998
出版商: OVID
关键词: inducible nitric oxide synthase;prostaglandin D2;vascular smooth muscle cells;expression inhibition;prostaglandin J2
数据来源: OVID
摘要:
&NA;Vascular smooth muscle cells (VSMCs) as well as macrophages have been shown to generate a substantial amount of NO in inflammatory vascular lesions. Prostaglandin (PG) D2(PGD2) is produced by inflammatory cells, including mast cells and macrophages. We investigated whether PGD2modulates NO metabolism in rat VSMCs. PGD2at a concentration of 10‐7mol/L or greater dose‐dependently inhibited nitrite accumulation in the medium of cultured VSMCs stimulated with interleukin 1 beta (IL‐1 beta). In a dose‐response analysis of IL‐1 beta and nitrite accumulation, PGD2was seen to decrease the maximal ability of VSMCs to generate NO, arguing against competition by PGD2at cytokine receptors. Northern analysis showed that PGD2suppresses induction of inducible NO synthase (iNOS) mRNA in IL‐1 beta‐stimulated VSMCs, with consequent inhibition of iNOS protein expression in Western analysis. A thromboxane A2(TXA2) analogue, U46619 (10‐5mol/L), produced less inhibition of NO generation than did PGD2. Neither the PGI2analog carbaprostacyclin nor PGE1showed any inhibition. PGD2dose‐dependently inhibited NO generation despite the addition of the TXA2antagonist SQ29548. PGJ2, Delta12‐PGJ2, and 15‐deoxy‐Delta12,14‐PGJ2, all metabolites of PGD2, were as potent as or slightly stronger than PGD2in the inhibition of NO generation. These data suggest that PGD2suppresses NO generation in VSMCs by inhibiting iNOS mRNA expression, most likely through the cascade of the PGJ2series rather than through the TX receptor or cAMP upregulation. Such action makes it likely that PGD2regulates NO metabolism in vascular lesions. (Circ Res. 1998;82:204‐209.)
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