IL-1beta during in vitro decidualization in primate.

Abstract

The sequence of biochemical and molecular events associated with decidualization in the primate remain unclear. In the baboon, the sequential changes during this period in vivo are characterized by the downregulation of alpha-smooth actin followed by induction of cyclooxygenase-2 (COX-2) at the implantation site and the expression of insulin growth factor binding protein-1 (IGFBP-1). IGFBP-1 is the predominant protein in decidualized cells and is considered to be biochemical marker of decidualization. In the baboon the expression of IGFBP-1 requires the presence of a conceptus in vivo or N(6), 2'-O-dibutyryladenosine 3:5'-cyclic monophosphate (dbcAMP) in the presence of hormones in vitro. In addition IL-1beta, as a possible conceptus-mediated factor, can induce IGFBP-1 expression in the presence of hormones following 3 days of incubation. However, if IL-1beta and dbcAMP are added together, IGFBP-1 expression is inhibited which resulted in IL-1beta being considered to be "inhibitory" to decidualization. Current data suggest that IL-1beta can activate multiple signaling pathways that either positively (no exogenous cAMP) or negatively (in presence of exogenous cAMP) regulate IGFBP-1 gene expression and decidualization in vitro. Signaling pathways activated by IL-1beta following 10 min of stimulation result in the phosphorylation of mitogen-activated protein kinase (MAPK, specifically p38 MAPK) and also lead to NF-kappaB activation. The expression of COX-2 and matrix metalloproteinase-3 (MMP-3) genes follows after 4-6 h. The steroid hormones, particularly progesterone, which are critical for IGFBP-1 expression, modulate the activity of IL-1beta by down-regulating MMP-3 activity. Disruption of actin filaments enhances IGFBP-1 induction during decidualization. IL-1beta induced MMP-3 may upregulate IGFBP-1 by initiation of cytoskeletal reorganization through degradation of extracellular matrix (ECM). Inhibition of IL-1beta induced pathways leads to reduction of IGFBP-1 expression, suggesting that IL-1beta may be involved in the events leading to decidualization in baboons.