ZFIN ID: ZDB-PUB-090914-4
TC1(C8orf4) is a novel endothelial inflammatory regulator enhancing NF-kappaB activity
Kim, J., Kim, Y., Kim, H.T., Kim, D.W., Ha, Y., Kim, J., Kim, C.H., Lee, I., and Song, K.
Date: 2009
Source: Journal of immunology (Baltimore, Md. : 1950)   183(6): 3996-4002 (Journal)
Registered Authors: Kim, Cheol-Hee, Kim, Hyun-Taek
Keywords: none
MeSH Terms:
  • Active Transport, Cell Nucleus
  • Animals
  • Cells, Cultured
  • Embryo, Nonmammalian
  • Endothelium, Vascular/pathology*
  • Humans
  • Inflammation/etiology*
  • Mice
  • NF-kappa B/metabolism*
  • Neoplasm Proteins/physiology*
  • Transcription Factor RelA/metabolism
  • Up-Regulation
  • Zebrafish
PubMed: 19684084 Full text @ J. Immunol.
Endothelial inflammation is regulated by a complex molecular mechanism. TC1(C8orf4) is a novel regulator implicated in cancer and inflammation. It is a small protein conserved well among vertebrates. In zebrafish embryos, it is mostly expressed in angio-hematopoietic system and the overexpression induces edema. In human aortic endothelial cells and umbilical vein endothelial cells, TC1 transfection up-regulates key inflammatory cytokines, enzymes, and adhesion proteins including IL-6, IL-1alpha, COX-2, CXCL1, CCL5, CCL2, IL-8, ICAM1, VCAM1, and E-selectin, while TC1 knockdown down-regulates them. TC1 also enhances inflammatory parameters such as monocyte-endothelial adhesion and endothelial monolayer permeability. TC1 is up-regulated by IL-1beta, TNF-alpha, LPS, and phorbol ester, and the up-regulation is inhibited by I-kappaB-kinase inhibitors. TC1, in turn, enhances the nuclear translocation of RelA and the DNA binding activity, suggesting a biological role of amplifying NF-kappaB signaling via a positive feedback. Our findings suggest that TC1 is a novel endothelial inflammatory regulator that might be implicated in inflammatory vascular diseases.