Suppression of interleukin 8 production by progesterone in rabbit uterine cervix.
Uterine cervical fibroblasts prepared from rabbits at 23 days of gestation were found to produce spontaneously the neutrophil chemotactic factor/interleukin 8 (IL-8). When the cells were treated with recombinant human interleukin 1 alpha and 1 beta (rhIL-1 alpha and -1 beta), both cytokines similarly enhanced the production of IL-8 in a dose-dependent manner. Recombinant tumour necrosis factor alpha also enhanced its production to a lesser extent, but interleukin 6 failed to modulate the production. Physiological concentrations of progesterone suppressed both the spontaneous and IL-1-mediated production of IL-8 in parallel with the decrease in the steady-state levels of its mRNA. These suppressive actions of progesterone were offset by co-treatment of cells with a progesterone antagonist, mifepristone (RU486). In conclusion, basal and IL-1-induced IL-8 production in rabbit uterine cervical fibroblasts is down-regulated by progesterone at the transcriptional level. These results obtained in vitro and our previous observations indicating that progesterone modulates the extra-cellular matrix breakdown via the suppression of production of matrix metalloproteinases and the augmentation of production matrix metalloproteinases and the augmentation of production of their specific inhibitors (TIMP-1) [Sato, Ito, Mori, Yamashita, Hayakawa and Nagase (1991) Biochem. J. 275, 645-650] may explain the mechanisms of the maintenance of pregnancy until parturition and the acceleration of uterine cervical ripening and dilatation at term.
Department of Biochemistry, Tokyo College of Pharmacy, Japan.
A
A
Ito
K
K
Imada
T
T
Sato
T
T
Kubo
K
K
Matsushima
Y
Y
Mori
D000818:Animals; D002584:Cervix Uteri / Q000187:drug effects* / Q000378:metabolism*; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics; D015735:Mifepristone / Q000494:pharmacology; D011247:Pregnancy / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004792:Enzyme Precursors; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015735:Mifepristone; D011374:Progesterone; D017364:Collagenases; D008666:Metalloendopeptidases; C022440:procollagenase; C048047:prostromelysin