THE INHIBITION OF SYNTHESIS OF A BETA-CHEMOKINE, MONOCYTE CHEMOTACTICPROTEIN-1 (MCP-1) BY PROGESTERONE

The control of chemokines in reproductive tissues has not been well ch aracterised. Progesterone plays a major part in many reproductive proc esses and an interaction between progesterone and the immune system ha s been postulated. MCP-1 is a beta chemokine that attracts and activat es macrophages, controls vascular smooth muscle cells, and can modulat e T helper cell cytokine production. MCP-1 may also play a role in rep roductive processes such as ovulation and parturition. MCP-1 synthesis is stimulated by the transcription factor NF-kappa B and is inhibited by glucocorticoid but the relevance of progesterone control in reprod uctive tissue is unknown. The effects of progesterone on the productio n in both choriodecidual cells and a breast cancer cell line T47D, whi ch expresses an oestrogen insensitive progesterone receptor, were inve stigated. A synthetic progestin (medroxyprogesterone acetate) inhibits choriodecidual cell production of MCP-1; this inhibition was reversed by the antiprogestin RU486. MCP-1 release from T47D cells can be stim ulated by IL-1 and this production is inhibited by progesterone with a n ED50 of less than 10(-9) M. A glucocorticoid (dexamethasone) had no effect on MCP-1 release in this system, suggesting that glucocorticoid receptor-mediated responses were impaired under these conditions. The se results demonstrate that an indirect effect of progesterone on the immune system is possible in reproductive tissues, whereby the initial effect of progesterone on epithelial or fibroblast cells would be tra nsmitted to leukocytes. (C) 1997 Academic Press.