Effects of platelet-activating factor on cytokine production by human uterine cervical fibroblasts

Effects of platelet-activating factor on cytokine production by human uterine cervical fibroblasts
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DOI:
10.1093/molehr/7.5.475
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发表时间:
2001-05-01
影响因子:
4
通讯作者:
Miyakawa, I
Miyakawa, I
中科院分区:
医学2区
文献类型:
--
作者:
Sugano, T;Narahara, H;Miyakawa, I

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血小板活化因子(PAF)是一种脂质,是一种强有力的促炎介质,参与包括分娩在内的多种生殖过程。为研究PAF对分娩前培养的人子宫颈成纤维细胞多种细胞因子表达的影响,进行了北方印迹分析和酶联免疫吸附试验。PAF的稳定类似物C-PAF以剂量依赖方式(10(-10)~ 10(-8)mol/l)增加IL-6和IL-8 mRNA的表达,在4 h内表达达高峰,培养液中相应蛋白浓度增加。10(-8)mol/l的C-PAF对单核细胞趋化蛋白-1 mRNA显示出明显的诱导作用,在4 h达到峰值,随后蛋白浓度增加。另一种细胞因子RANTES(正常T细胞表达和分泌的受激活调节的细胞因子)在10(-8)mol/l的C-PAF作用下显示出明显的mRNA诱导作用,并以时间依赖的方式持续增加,直至24 h。PAF诱导的细胞因子产生被PAF受体特异性拮抗剂WEB 2170阻断。PAF可刺激局部细胞因子的产生,从而诱导白细胞迁移并加速宫颈中的胶原溶解,从而有助于分娩期间的宫颈成熟。
Platelet-activating factor (PAF), a lipid that acts as a potent proinflammatory mediator, is involved in several reproductive processes including parturition, To investigate the effects of PAF on expression of various cytokines by cultured human uterine cervical fibroblasts obtained at term prior to labour, Northern blot analyses and enzyme-linked immunosorbent assays were performed. C-PAF, a stable analogue of PAF, increased expression of interleukin-6 and -8 mRNA in a dose-dependent manner (10(-10) to 10(-8) mol/l of C-PAF), and the expression peaked within 4 h, The corresponding protein concentrations were increased in culture media. Monocyte chemoattractant protein-1 mRNA showed marked induction by 10(-8) mol/l of C-PAF; this peaked by 4 h and was followed by an increase in the protein concentration. Another cytokine, RANTES (regulated upon activation, normal T cell expressed and secreted) showed marked mRNA induction by 10(-8) mol/l of C-PAF, and continued to increase in a time-dependent manner until 24 h, The protein concentration was correspondingly increased in the medium. The PAF-induced cytokine production was abolished by co-incubation with WEB 2170, a specific PAF receptor antagonist. PAF may stimulate local production of cytokines which may induce migration of leukocytes and accelerate collagenolysis in the uterine cervix, thus contributing to cervical ripening during parturition.