MODULATION OF THE LEVELS OF INTERLEUKIN-8 MESSENGER-RIBONUCLEIC-ACID AND INTERLEUKIN-8 PROTEIN-SYNTHESIS IN HUMAN ENDOMETRIAL STROMAL CELLSBY TRANSFORMING GROWTH-FACTOR-BETA-1

Selected functions of uterine endometrium of ovulatory women before an d during pregnancy appear to be modulated by cytokines and other parac rine-acting factors. Some of these functions are regulated, in turn, b y cyclic changes in ovarian steroid secretion or by pregnancy-induced endocrine and paracrine factors. The recruitment of specific types and numbers of bone marrow-derived cells into the endometrium occurs in a predictable manner with hormonal changes of the ovarian cycle, during the process of endometrial decidualization, at the time of blastocyst implantation, and during pregnancy, parturition, and the puerperium. As part of an investigation of the regulation of the leukocyte populat ion of endometrium/decidua, this study was conducted to evaluate furth er the regulation of interleukin-8 (IL-8) gene expression by transform ing growth factor-beta (TGF beta). IL-8 is a neutrophil chemoattractan t/activating and T cell chemotactic factor as well as a chemotactic fa ctor for fibroblasts. IL-8 is produced by mesenchymal cells of many ti ssues, including human endometrial stromal cells in culture. The level of IL-8 messenger ribonucleic acid (mRNA) in endometrial stromal cell s and the accumulation of immunoreactive IL-8 in medium are increased by TGF beta 1 treatment of these cells. This response to TGF beta 1 is attributable primarily to an increase in the stability of IL-8 mRNA t hrough a process that is dependent on protein synthesis. Transcription of the IL-8 gene in endometrial stromal cells is not increased, but, rather, is slightly decreased, by treatment with TGF beta 1. The findi ngs of this study indicate that TGF beta may act in endometrial stroma to modulate the stability of IL-8 mRNA.