TC1(C8orf4) is a novel endothelial inflammatory regulator enhancing NF-kappaB activity.
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.
Kim
Jungtae
J
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Kim
Yunlim
Y
Kim
Hyun-Taek
HT
Kim
Dong Wook
DW
Ha
Yunhi
Y
Kim
Jihun
J
Kim
Cheol-Hee
CH
Lee
Inchul
I
Song
Kyuyoung
K
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000502:physiology*; D051996:Transcription Factor RelA / Q000378:metabolism; D015854:Up-Regulation; D015027:Zebrafish
D016328:NF-kappa B; D009363:Neoplasm Proteins; C534905:Tcim protein, mouse; D051996:Transcription Factor RelA