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J Biol Chem. 2012 Nov 9;287(46):38913-21. doi: 10.1074/jbc.M112.388389. Epub 2012 Sep 20.

The TG-interacting factor TGIF1 regulates stress-induced proinflammatory phenotype of endothelial cells.

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1
Laboratory of Radiopathology and Experimental Therapeutics, Institute for Radiological Protection and Nuclear Safety, 92262 Fontenay-aux-Roses, France.

Abstract

The endothelium contributes to the control of the tissue inflammatory response following stress and in particular after exposure to ionizing radiation. We previously showed that the TG-interacting factor 1 (TGIF1) plays a role in radiation-induced normal tissue injury. In this study we hypothesized that this protein could play a role in inflammation. The role of TGIF1 in the stress-induced proinflammatory phenotype was investigated in human endothelial cells. In HUVECs ionizing radiation induces TGIF1 expression as well as a proinflammatory phenotype associated with up-regulation of IL-6, IL-8, CXCL1, MIP-2, and MCP-1. TGIF1 overexpression enhances the radiation-induced proinflammatory phenotype whereas TGIF1 silencing limits both the TNF-α- and radiation-induced overexpression of proinflammatory cytokines. Interestingly, in vivo, in radiation-induced intestinal inflammation in mice, TGIF1 genetic deficiency is associated with a reduced radiation-induced overexpression of proinflammatory molecules. In HUVECs, TNF-α- and radiation-induced NF-κB pathway activation is not influenced by TGIF1 expression, whereas TGIF1 knockdown inhibits both TNF-α- and radiation-induced p38 MAPK pathway activation. This study demonstrates that TGIF1 plays a role in TNF-α- and radiation-induced inflammation and suggests that it could be a target in limiting this event in the vascular compartment.

PMID:
22995913
PMCID:
PMC3493932
DOI:
10.1074/jbc.M112.388389
[Indexed for MEDLINE]
Free PMC Article
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