REGULATION OF INTERLEUKIN-8 GENE-EXPRESSION IN HUMAN ENDOMETRIAL CELLS IN CULTURE

In this study, we investigated the regulation of interleukin-8 (IL-8) gene expression in separated endometrial stromal and epithelial cells of human endometrium. This research was conducted as part of an analys is of the role of these cells in regulating the recruitment of leukocY tes to the endometrium. Well-characterized model systems were used to study the regulation of endometrial IL-8 gene expression, namely, stro mal cells in monolayer culture after first passage and glandular epith elium in primary culture. The levels of IL-8 mRNA and the accumulation of immunoreactive IL-8 in the medium of endometrial stromal cells is culture increased in a time- and concentration-dependent manner upon t reatment with IL-1alpha, tumor necrosis factor-alpha ,or serum. The ef fects of IL-1alpha plus serum on IL-8 mRNA levels were at least additi ve. Serum treatment caused a modest stimulation of IL-8 gene transcrip tion (evaluated after 6 h of treatment) in endometrial stromal cells, but serum also acted in these stromal cells to prolong the half-life o f IL-8 mRNA by more than 2.5-fold. The regulation of the levels of IL- 8 mRNA in endometrial epithelial cells is distinctly different from th at in stroma. First, the levels of IL-8 mRNA in non-treated epithelial cells in serum-free medium were much greater than those in stromal ce lls under similar conditions. Second, whereas the levels of IL-8 mRNA in endometrial epithelial cells also increased in response to serum an d to IL-1 in the absence of serum, in the presence of serum, IL-1 trea tment caused no appreciable change in the levels of IL-8 mRNA as was t he case in endometrial stromal cells.