Differential effects of interleukin-1β and transforming growth factor-β1 on the expression of the inflammation-associated protein, ADAMTS-1, in human decidual stromal cells in vitro

BACKGROUND: The pro-inflammatory cytokine, interleukin-1 beta (IL-1 beta) promotes the proteolytic degradation of the extracellular matrix (ECM) of maternal decidua, a critical step in pregnancy that is counterbalanced by the expression of the anti-inflammatory cytokine, transforming growth factor-beta 1 (TGF-beta 1). Recently, the inflammation-associated protein, ADAMTS-1, a member of the ADAMTS (A Disintegrin Metalloproteinase with ThromboSpondin repeats) gene family of metalloproteinases has been assigned a central role in the formation and organization of tissues. In view of these observations, we have hypothesized that ADAMTS-1 contributes to the cytokine-mediated remodelling of decidual ECM. METHODS: The spatiotemporal expression of ADAMTS-1 in human endometrium was examined by immunohistochemistry. A quantitative-competitive (QC)-PCR strategy and western blot analysis was then employed to determine whether IL-1 beta and TGF-beta 1 regulate ADAMTS-1 mRNA and protein expression levels in primary cultures of stromal cells isolated from first trimester decidua. RESULTS: ADAMTS-1 expression is associated with decidualization of the endometrial stroma in vivo. IL-1 beta increased whereas TGF-beta 1 decreased ADAMTS-1 mRNA and protein levels in decidual stromal cell cultures in a concentration- and time-dependent manner. These regulatory effects were attenuated by function-perturbing antibodies specific for either cytokine. CONCLUSION: IL-1 beta and TGF-beta 1 differentially regulate ADAMTS-1 expression in human decidual stromal cells.