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Reproduction (2007) 134 811-822
DOI: 10.1530/REP-07-0289
Copyright © 2007 Society for Reproduction and Fertility
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RESEARCH

Identification of interleukin-1ß regulated genes in uterine smooth muscle cells

Grégory Chevillard1,2, Anna Derjuga1, Dominic Devost3, Hans H Zingg3 and Volker Blank1,2,4

1 Lady Davis Institute for Medical Research, 2 Department of Medicine, 3 Department of Pharmacology and 4 Department of Physiology, McGill University, 3755 Cote Sainte-Catherine Road, Montreal, Quebec, H3T 1E2 Canada

Correspondence should be addressed to V Blank; Email: volker.blank{at}mcgill.ca

We analyzed the response of uterine smooth muscle cells to interleukin-1ß (IL-1ß). We first showed that PHM1-31 myometrial cells, our cellular model, are contractile. To determine the molecular mechanisms of uterine smooth muscle cell activation by proinflammatory cytokines, we performed genechip expression array profiling studies of PHM1-31 cells in the absence and the presence of IL-1ß. In total, we identified 198 known genes whose mRNA levels are significantly modulated (> 2.0-fold change) following IL-1ß exposure. We confirmed the expression changes for selected genes by independent mRNA and protein analysis. The group of genes induced by IL-1ß includes transcription factors and inflammatory response genes such as nuclear factor of {kappa} light polypeptide gene enhancer in B-cells (NF{kappa}B), pentraxin-related gene (PTX3), and tumor necrosis factor {alpha}-induced protein 3/A20 (TNFAIP3/A20). We also found up-regulation of chemokines like C-X-C motif ligand 3 (CXCL3) and extracellular matrix remodeling signaling molecules like tenascin C (TNC). Our data suggest that IL-1ß elicits the rapid activation of a cellular network of genes particularly implicated in inflammatory response that may create a cellular environment favorable for myometrial cell contraction. Our results provide novel insights into the mechanisms of uterine smooth muscle cell regulation and possibly infection-induced preterm labor.




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