title: The TG-interacting factor TGIF1 regulates stress-induced proinflammatory phenotype of endothelial cells.
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.
authors.affiliation: Laboratory of Radiopathology and Experimental Therapeutics, Institute for Radiological Protection and Nuclear Safety, 92262 Fontenay-aux-Roses, France.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hneino
authors.forename: Karl
authors.initials: K
authors.lastname: Blirando
authors.forename: Valérie
authors.initials: V
authors.lastname: Buard
authors.forename: Georges
authors.initials: G
authors.lastname: Tarlet
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.forename: Pamela
authors.initials: P
authors.lastname: Hoodless
authors.forename: Agnès
authors.initials: A
authors.lastname: François
authors.forename: Fabien
authors.initials: F
authors.lastname: Milliat
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011839:Radiation, Ionizing; D012097:Repressor Proteins / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D051785:Smad Proteins; C097504:TGIF1 protein, human; C490797:Tgif1 protein, mouse; D014409:Tumor Necrosis Factor-alpha