The role of nitric oxide in PGI_2 production by human pulmonary artery smooth muscle cells

一氧化氮在人肺动脉平滑肌细胞产生PGI_2中的作用

• 批准号: 09670636
• 负责人: WATANABE Kentaro
• 金额: $ 1.09万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670636/
• 关键词: human pulmonary artery smooth muscle cells; prostacyclin(PGI_2); nitric oxide(NO,nitrogen monooxide); cytokines; lipopolysaccharide(LPS); IL-6; 1L-6

Human pulmonary arlcry smooth musclc cclls(HPASMC) were isolated and culfured from autopsy materials, and the effect of nitric oxide(NO) on PG12 production by HPASMC was examined and the effect of IL-6 on NO production by HPASMC was also examined to elucidate the relationship of the production of NO and proslaglandins by H PASMC.1)LPS, IL-1beta and TNF_2 enhanced the production of NO by HPASMC.2)The enlhanced production of PGI_2 by LPS-and IL-1beta-treated HPASMC was further augmenter when HPASMC were treated with LPS or IL-1beta together with sodium nitroprusside.3)The enhanced production of PGI_2 by LPS- and IL-1beta-treated HPASMC was attenuated when HPASMC were treated with LPS or IL-1beta together with L-NMMA.4)Methylene blue(MeB) suppressed PGI_2 production by HPASM C, and attenuated the enhanced production of PGI_2 by HPASMC treated with LPS or IL-1beta.5)Although IL-6 did not changed the basal production of NO by HPASMC, it attenuated the enhanced production of NO by HPASMC treated with LPS or IL-1beta.6)LPS, IL-1beta, TNF_2 and SNP up to the maximum concentrations used in these experiments did not increase thc LDH release from HPASMC treated with these agents.From these experimental lindings it is suggested that(1)NO enhances PGI_2 production by human pulmonary arlery smooth muscle cells.(2)IL-6 suppresses not only the production of prostagland ins but NO by human pulmonary artery smooth muscle cells. this result could show antiinllammatory aspect of IL-6 in vivo.(3)Pulmonary artery smooth lb muscles could actively participate in the regulation of pumonary blood flow and tonus of pulmonary artery by the interaction of NO and prostaglandins.Further examinations are needed to elucidate the. mechanisms of NO-mediated enhancement of PGl_2 production and IL-6-mediated suppression of NO production by examining the induction of COX-2 and iNOS proteins and genes.

从尸检材料中分离培养人肺动脉平滑肌细胞（HPASMC），考察一氧化氮（NO）对HPASMC产生PG12的影响，并考察IL-6对HPASMC产生NO的影响。 H PASMC 产生 NO 和前列腺素的关系。 1)LPS、IL-1β 和 TNF_2 通过以下方式增强 NO 的产生HPASMC.2) 当用 LPS 或 IL-1β 与硝普钠一起处理 HPASMC 时，经 LPS 和 IL-1β 处理的 HPASMC 增强的 PGI_2 产生进一步增强。3) LPS- 和 IL- 增强的 PGI_2 产生当 HPASMC 用 LPS 或 IL-1β 与 L-NMMA 一起处理时，1beta 处理的 HPASMC 减弱。4）亚甲蓝（MeB）抑制 HPASM C 产生 PGI_2，并减弱经 LPS 或 IL-1beta 处理的 HPASMC 增强的 PGI_2 产生。 5）虽然 IL-6 没有改变 HPASMC 的 NO 基础产生，但它减弱了 HPASMC 增强的 NO 产生用 LPS 或 IL-1beta 处理。6)LPS、IL-1beta、TNF_2 和 SNP 直至这些实验中使用的最大浓度并没有增加 thc用这些试剂处理的 HPASMC 释放 LDH。从这些实验结果表明，(1)NO 增强人肺动脉平滑肌细胞的 PGI_2 产生。(2)IL-6 不仅抑制前列腺素的产生，还抑制人的 NO 产生肺动脉平滑肌细胞。 (3)肺动脉平滑肌可通过NO与前列腺素的相互作用积极参与肺血流和肺动脉张力的调节，有待进一步研究证实。这。通过检查COX-2和iNOS蛋白和基因的诱导，研究NO介导的PG1_2产生增强和IL-6介导的NO产生抑制的机制。

项目成果

渡辺憲太郎: "血管内皮細胞・平滑筋のプロスタグランディン代謝" Progress in Medicine. 19(1). 222-232 (1999)

Kentaro Watanabe：“血管内皮细胞和平滑肌中的前列腺素代谢”，医学进展 19(1)。

FQ Wen,K Watanabe,M Yoshida: "Eicosanoid profile in cultured human pulmonary artery smooth muscle cells treated with IL-1β and TNFα" Prostaglandins Leukotrienes and Essential Fatty Acid. (in press).

FQ Wen、K Watanabe、M Yoshida：“用 IL-1β 和 TNFα 处理的培养人肺动脉平滑肌细胞中的类二十烷酸谱”前列腺素白三烯和必需脂肪酸（正在出版）。

FQ Wen, K Watanabe, M Yoshida: "Lipopolysaccharide enhances the release of arachidonic acid metabolites in cultured human pulmonary artery smooth muscle cells" Artery,. (in press).

FQ Wen、K Watanabe、M Yoshida：“脂多糖增强培养的人肺动脉平滑肌细胞中花生四烯酸代谢物的释放”Artery，。

FQ Wen, K Watanabe, M Yoshida: "Lipopolysaccharide enhances the release of arachidonic acid metabolites in cultured human pulmonary artery smooth muscle cells" Artery, in press.

FQ Wen、K Watanabe、M Yoshida：“脂多糖增强培养的人肺动脉平滑肌细胞中花生四烯酸代谢物的释放”《Artery》，出版中。