The role of cytokines on the production of NO and PGI2 by human pulmonary artery smooth muscle and endothelial cells

细胞因子对人肺动脉平滑肌和内皮细胞产生NO和PGI2的作用

基本信息

批准号：
07670686
负责人：
WATANABE Kentaro
金额：
$ 1.54万
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：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670686/
关键词：
pulmonary artery smooth muscle cells prostacyclin (PGI_2)nitric oxide (NO,nitrogen monooxide)cytokines lipopolysaccharide (LPS)NO donor NO synthase inhibitor プロスタサイクリン NO サイトカン一酸化窒素(NO)

项目摘要

Human pulmonary artery smooth muscle cells (HAPSMC) were cultured from autopsy materials, and the effect of lipopolysaccharide (LPS) and cytokines on PGI_2 production and arachidonic acid metabolism by HPASMC was examined.1) LPS,IL-1_<beta> and TNF_<alpha> enhanced the production of PGI_2 and nitric oxide (NO) by HPASMC.2) HPLC analysis revealed that 10mug/ml of LPS and 200U/ml of IL-1_<beta> enhanced the production of both lipoxygenase (LO) and cyclooxygenase (COX) products, and 500U/ml of TNFalpha enhanced that of COX products.3) IL-6 suppressed the basal production of PGI_2 by HPASMC,and attenuated the enhancement of PGI_2 production by HPASMC treated with LPS,IL-1_<beta> or TNF_<alpha>.4) The enhancement of PGI_2 production by LPS and IL-1_<beta> was attenuated when HPASMC were treated with LPS or IL-1_<beta> together with L-NMMA,NO synthase inhibitor.5) The enhancement of PGI_2 production by LPS and IL-1_<beta> was augmented when HPASMC were treated with LPS or IL-1_<beta> together with sodium nitroprusside, NO donor.6) From these experimental findings, it is suggested that(1) Human pulmonary artery smooth muscle cells could produce NO and PGI_2 in response to LPS or cytokines.(2) NO could enhance the production of PGI_2 by pulmonary artery smooth muscle cells(3) Pulmonary srtery smooth muscles could actively participate in the regulation of pulmonary blood flow and tonus of pulmonary artery by producing NO and PGI_2.Further examination is needed to elucidate the mechanism of the enhancement of PGI_2 production by NO.

从尸检材料中培养人肺动脉平滑肌细胞（HAPSMC），考察脂多糖（LPS）和细胞因子对HPASMC产生PGI_2和花生四烯酸代谢的影响。1）LPS、IL-1_<β>和TNF_< α> 增强 HPASMC 产生的 PGI_2 和一氧化氮 (NO)。2) HPLC 分析显示 10mug/ml 的 LPS 和200U/ml的IL-1_β增强了脂氧合酶(LO)和环氧合酶(COX)产物的产生，500U/ml的TNFα增强了COX产物的产生。3)IL-6通过以下方式抑制PGI_2的基础产生： HPASMC，并减弱了用 LPS、IL-1_<beta> 或 LPS 处理的 HPASMC 对 PGI_2 产生的增强作用TNF_α.4)当用LPS或IL-1_β与L-NMMA、NO合酶抑制剂一起处理HPASMC时，LPS和IL-1_β对PGI_2产生的增强减弱。5)增强当用LPS或IL-1_β与硝普钠、NO供体一起处理HPASMC时，LPS和IL-1_β产生的PGI_2增加。6)这些实验结果表明：(1)人肺动脉平滑肌细胞可以响应LPS或细胞因子产生NO和PGI_2。(2)NO可以增强肺动脉平滑肌细胞产生PGI_2(3)肺动脉平滑肌细胞动脉平滑肌可通过产生NO和PGI_2积极参与肺血流和肺动脉张力的调节。NO增强PGI_2产生的机制还需进一步研究。