REGULATION OF MONOCYTE CHEMOTACTIC PROTEIN-1 GENE-EXPRESSION IN HUMAN ENDOMETRIAL CELLS IN CULTURES

Bone marrow-derived leukocytes are present in human endometrium/decidua and are believed to serve a variety of functions in this tissue. The number and type of leukocytes in endometrium/decidua vary with the hormonal milieu of the ovarian cycle, with blastocyst implantation, and during pregnancy. The factors that regulate the recruitment of specific leukocytes to the endometrium and those that modulate the function or replication of leukocytes in this tissue are not well defined. In this study, we evaluated the potential for synthesis of monocyte chemotactic protein-1 (MCP-1), a polypeptide with monocyte/macrophage chemotactic and activating properties, in human endometrium and in separated endometrial stromal and epithelial cells. MCP-1 mRNA was readily detected by northern analysis of total RNA isolated from human endometrial tissue (n= 39 tissues from ovulatory women; n = 3 atrophic endometria from anovulatory women; n = 6 from women ingesting oral contraceptives or medroxyprogesterone acetate) and decidua parietalis at midtrimester (n = 6 pregnancies) and at term (n = 6 pregnancies). The levels of MCP-1 mRNA varied considerably among tissues; but in this relatively small number of samples, there was no apparent relationship between day of cycle, endocrine status, or duration of pregnancy and the level of MCP-1 mRNA. MCP-1 mRNA was detected in separated endometrial stromal cells and epithelial cells in culture. In confluent human endometrial stromal cells in the absence or presence of fetal bovine serum (10%, v/v), MCP-1 mRNA was detected by northern analysis of total RNA. Fetal bovine serum effected a concentration-dependent decrease in the levels of MCP-1 mRNA. The level of MCP-1 mRNA in endometrial stromal cells maintained in serum-free medium increased in a time- and concentration-dependent manner in response to treatment with interleukin-1 alpha or tumor necrosis factor-alpha. Platelet-derived growth factor and interferon-alpha also acted, in a concentration-dependent manner, to increase the level of MCP-1 mRNA.