PLATELET-DERIVED GROWTH-FACTOR SUPPRESSES AND FIBROBLAST GROWTH-FACTOR ENHANCES CYTOKINE-INDUCED PRODUCTION OF NITRIC-OXIDE BY CULTURED SMOOTH-MUSCLE CELLS - EFFECTS ON CELL-PROLIFERATION
PLATELET-DERIVED GROWTH-FACTOR SUPPRESSES AND FIBROBLAST GROWTH-FACTOR ENHANCES CYTOKINE-INDUCED PRODUCTION OF NITRIC-OXIDE BY CULTURED SMOOTH-MUSCLE CELLS - EFFECTS ON CELL-PROLIFERATION
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DOI：
10.1161/01.res.71.5.1088
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发表时间：
1992-11-01
影响因子：
20.1
通讯作者：
VANHOUTTE, PM
中科院分区：
文献类型：
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作者：
SCOTTBURDEN, T;SCHINI, VB;VANHOUTTE, PM
碱性成纤维细胞生长因子或表皮生长因子对培养的静止的平滑肌细胞(大鼠和人)的胸腺嘧啶核苷掺入的刺激作用可被在吲哚美辛存在下与IL-1β同时处理而减弱。在相似的实验条件下，细胞因子不能抑制血小板衍生生长因子-AB和-BB诱导的胸腺嘧啶核苷掺入。培养上清液中亚硝酸盐水平的升高与胸腺嘧啶核苷掺入的抑制有关。血小板衍生生长因子-AB和-BB抑制同时用白介素1β和生长因子处理的细胞产生一氧化氮(以条件培养液中的亚硝酸盐水平衡量)。然而，血小板衍生生长因子-AA既不影响平滑肌细胞亚硝酸盐的产生，也不影响胸腺嘧啶核苷的掺入。成纤维细胞生长因子或表皮生长因子的存在协同增加了细胞因子刺激的平滑肌细胞亚硝酸盐的产生。在硝基-L-精氨酸存在下，对胸腺嘧啶核苷掺入的抑制和伴随的亚硝酸盐生成的增加被取消。在低浓度细胞因子存在下培养9天后，细胞生长受到抑制，而添加硝基-L-精氨酸则相反。在与其他静止的细胞层结合之前，对与细胞因子共培养的平滑肌细胞进行处理，以诱导一氧化氮的产生，导致第二层细胞抑制胸腺嘧啶核苷的掺入，而不考虑用于刺激的生长因子。一氧化氮可能是血管壁内平滑肌细胞增殖的内源性抑制因子，其产生的障碍可能是强大的血管有丝分裂原如血小板衍生生长因子的作用之一。
Stimulation of thymidine incorporation by basic fibroblast growth factor or epidermal growth factor treatment of cultured quiescent smooth muscle cells (rat and human) was attenuated by the concomitant treatment with interleukin-1beta in the presence of indomethacin. Platelet-derived growth factor-AB and -BB-induced thymidine incorporation was not inhibited by the presence of the cytokine under similar experimental conditions. Elevation of nitrite levels in the conditioned medium of cultures exposed to interleukin-1beta correlated with the inhibition of thymidine incorporation. Platelet-derived growth factor-AB and -BB inhibited the production of nitric oxide (measured as nitrite levels in conditioned medium) by cells treated simultaneously with interleukin-1beta and growth factor. However, platelet-derived growth factor-AA neither affected nitrite production nor thymidine incorporation by smooth muscle cells. Levels of cytokine-stimulated nitrite production by smooth muscle cells were increased synergistically by the presence of fibroblast growth factors or epidermal growth factor. The inhibition of thymidine incorporation and concomitant elevation of nitrite production was abolished in the presence of nitro-L-arginine. Cultures maintained in the presence of low levels of the cytokine for 9 days were growth-inhibited, and this was reversed when culture medium was supplemented with nitro-L-arginine. The treatment of smooth muscle cells, which were grown in coculture inserts with the cytokine to induce nitric oxide production, before their combination with other quiescent layers of cells resulted in the inhibition of thymidine incorporation by this second layer of cells regardless of the growth factor used for stimulation. Nitric oxide may act as an endogenous inhibitor of smooth muscle cell proliferation in the vessel wall, and impairment of its production may be one action of potent vascular mitogens such as platelet-derived growth factor.