The inhibition of synthesis of a beta-chemokine, monocyte chemotactic protein-1 (MCP-1) by progesterone.
The control of chemokines in reproductive tissues has not been well characterised. Progesterone plays a major part in many reproductive processes and an interaction between progesterone and the immune system has been postulated. MCP-1 is a beta chemokine that attracts and activates macrophages, controls vascular smooth muscle cells, and can modulate T helper cell cytokine production. MCP-1 may also play a role in reproductive 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 reproductive tissue is unknown. The effects of progesterone on the production in both choriodecidual cells and a breast cancer cell line T47D, which expresses an oestrogen insensitive progesterone receptor, were investigated. 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 stimulated by IL-1 and this production is inhibited by progesterone with an 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. These 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 transmitted to leukocytes.
Kelly
R W
RW
Medical Research Council Reproductive Biology Unit, Department of Obstetrics and Gynaecology, University of Edinburgh Centre for Reproductive Biology, United Kingdom.
Carr
G G
GG
Riley
S C
SC
D001943:Breast Neoplasms / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D019742:Chemokines, CC / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D002823:Chorion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D011374:Progesterone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018932:Chemokine CCL2; D019742:Chemokines, CC; D011374:Progesterone