Progestin regulation of interleukin-8 mRNA levels and protein synthesis in human endometrial stromal cells.

The migration of leukocytes into the human endometrium is a normal occurrence that appears to be linked to the hormonal events of the ovarian cycle. In addition, the appearance of large numbers of leukocytes in decidua accompanies normal human pregnancy and puerperal endometrial repair during uterine involution. These leukocytic investments in endometrial-decidual function are also affected by external stimuli, e.g. infection. The formation of cytokines and the response of the uterine endometrium and decidua to cytokines is likely to be an important function of this tissue before, during and soon after pregnancy. Because interleukin-8 (IL-8) is a chemo-attractant activating factor for neutrophils and T cells, the possibility was considered that IL-8 may participate in endometrial leukocytic infiltration in a manner that is hormonally regulated. Previously, we found that IL-8 mRNA is present in the endometrium and decidual tissues; and, using human endometrial stromal cells in monolayer culture as a model system, we found that IL-1 and tumor necrosis factor-alpha act in a time- and concentration-dependent manner to increase IL-8 mRNA and the accumulation of immunoreactive (ir)IL-8 protein. In this study, we found that progesterone and a synthetic progestin, medroxyprogesterone acetate (MPA) act to enhance the action of IL-1 to increase the level of IL-8 mRNA; this action of progesterone/MPA appears to be affected principally by the stabilization of IL-8 mRNA, together with a small increase in IL-8 gene transcription.