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

Platelet-activating factor (PAF), a lipid that acts as a potent proinflamma tory mediator, is involved in several reproductive processes including part urition, To investigate the effects of PAF on expression of various cytokin es 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 interl eukin-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 con centrations were increased in culture media. Monocyte chemoattractant prote in-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 c ytokine, RANTES (regulated upon activation, normal T cell expressed and sec reted) 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 concentrati on was correspondingly increased in the medium. The PAF-induced cytokine pr oduction was abolished by co-incubation with WEB 2170, a specific PAF recep tor antagonist. PAF may stimulate local production of cytokines which may i nduce migration of leukocytes and accelerate collagenolysis in the uterine cervix, thus contributing to cervical ripening during parturition.