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Vascul Pharmacol. 2013 Jul-Aug;59(1-2):36-43. doi: 10.1016/j.vph.2013.06.001. Epub 2013 Jun 6.

Selective suppression of endothelial cytokine production by progesterone receptor.

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  • 1Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues.

Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

4′,6-diamidino-2-phenylindole; DAPI; HUVEC; Immune cell; Inflammation; LPS; PR; PRKO; Reproduction; Steroid hormone; hPR; human progesterone receptor; human umbilical vein endothelial cell; lipopolysaccharide; progesterone receptor; progesterone receptor knockout

PMID:
23747964
[PubMed - indexed for MEDLINE]
PMCID:
PMC3819224
Free PMC Article

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