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Hum. Reprod. Advance Access originally published online on May 4, 2006
Human Reproduction 2006 21(8):1990-1999; doi:10.1093/humrep/del108
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Differential effects of interleukin-1beta and transforming growth factor-beta1 on the expression of the inflammation-associated protein, ADAMTS-1, in human decidual stromal cells in vitro

York Hunt Ng1, Hua Zhu1, Catherine J. Pallen2, Peter C.K. Leung1 and Colin D. MacCalman1,3

1 Department of Obstetrics and Gynecology and 2 Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada

3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Room I3091-950, West 28th Avenue, Vancouver, BC, Canada V5Z 4H4. E-mail: cdmaccalman{at}hotmail.com

BACKGROUND: The pro-inflammatory cytokine, interleukin-1 beta (IL-1beta) 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-beta1). Recently, the inflammation-associated protein, ADAMTS-1, a member of the ADAMTS (A Disintegrin And 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-1beta and TGF-beta1 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-1beta increased whereas TGF-beta1 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-1beta and TGF-beta1 differentially regulate ADAMTS-1 expression in human decidual stromal cells.

Key words: ADAMTS-1/decidua/interleukin-1beta/pregnancy/transforming growth factor-beta1


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