PROGESTIN REGULATION OF INTERLEUKIN-8 MESSENGER-RNA LEVELS AND PROTEIN-SYNTHESIS IN HUMAN ENDOMETRIAL STROMAL CELLS

The migration of leukocytes into the human endometrium is a normal occ urrence that appears to be linked to the hormonal events of the ovaria n 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 endo metrial-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 func tion of this tissue before, during and soon after pregnancy. Because i nterleukin-8 (IL-8) is a chemo-attractant activating factor for neutro phils and T cells, the possibility was considered that IL-8 may partic ipate in endometrial leukocytic infiltration in a manner that is hormo nally regulated. Previously, we found that IL-8 mRNA is present in the endometrium and decidual tissues; and, using human endometrial stroma l cells in monolayer culture as a model system, we found that IL-I and tumor necrosis factor-alpha act in a time- and concentration-dependen t manner to increase IL-8 mRNA and the accumulation of immunoreactive (ir)IL-8 protein. In this study, we found that progesterone and a synt hetic progestin, medroxyprogesterone acetate (MPA) act to enhance the action of IL-1 to increase the level of IL-8 mRNA; this action of prog esterone/MPA appears to be affected principally by the stabilization o f IL-8 mRNA, together with a small increase in IL-8 gene transcription . Copyright (C) 1996 Published by Elsevier Science Ltd.