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Interleukin-1ß Induces the Expression of Insulin-Like Growth Factor Binding Protein-1 during Decidualization in the Primate¹

Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, Illinois 60212-7313

Address all correspondence and requests for reprints to: Asgi T. Fazleabas, Ph.D., The University of Illinois at Chicago, Department of Obstetrics and Gynecology, 820 South Wood Street (M/C 808), Chicago, Illinois 60612-7313. E-mail: asgi{at}uic.edu

Since interleukin (IL)-1 can modulate fetal/maternal interactions, we hypothesized that IL-1ß is one potential embryonic cytokine that regulates the conceptus-induced decidual response in baboon stromal fibroblasts. Treatment of stromal fibroblasts with IL-1ß (10 ng/ml, 10 min) resulted in the phosphorylation of p38 mitogen-activated protein kinase and IB-. This suggests that IL-1ß induces multiple signaling pathways in stromal cells that result in the activation of mitogen-activated protein kinase cascade and the transcription factor NF-B. After 4 h of stimulation, IL-1ß induced gene expression of cyclooxygenase-2 (COX-2) but not cyclooxygenase-1 (COX-1). PGE₂ synthesis paralleled COX-2 messenger RNA expression. The addition of hormones [36 nM estradiol-17ß, 1 µM medroxyprogesterone acetate, and 100ng/ml relaxin] to IL-1ß-treated cells induced insulin-like growth factor binding protein-1 (IGFBP-1) messenger RNA expression after 3 days of incubation. A specific COX-2 inhibitor, NS 398 (10 nM), partially inhibited IGFBP-1 protein synthesis. In contrast, the induction of IGFBP-1 by N⁶, 2'-O-dibutyryladenosine 3:5'-cyclic monophosphate (dbcAMP) and hormones was not affected by NS 398 treatment. Both dbcAMP and IL-1ß, in the presence of hormones, can independently induce IGFBP-1 gene expression and decidualization. However, if IL-1ß and dbcAMP were added together, IGFBP-1 expression was inhibited. These data suggest that IL-1ß can activate multiple signaling pathways that either positively or negatively regulate IGFBP-1 gene expression and decidualization.

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