Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells.
TWEAK, a member of the TNF family, induces cell death in some tumor cell lines, but also induces proliferation of endothelial cells and angiogenesis. Recently, fibroblast growth factor-inducible 14 (Fn14) has been identified to be a TWEAK receptor, which may be responsible for the proliferation of endothelial cells and angiogenesis. In this study, we investigated the pro-inflammatory effect of TWEAK on human umbilical vein endothelial cells (HUVEC). We demonstrated that TWEAK could not only induce the proliferation and migration but also upregulate the cell surface expression of adhesion molecules such as ICAM-1 and E-selectin, and induce the secretion of chemokines such as IL-8 and MCP-1 in HUVEC. Moreover, by using an anti-Fn14 mAb that blocks the TWEAK/Fn14 interaction, we demonstrated that Fn14 was constitutively expressed on HUVEC and totally mediated the biological effects of TWEAK on HUVEC. These results indicated that TWEAK could induce pro-inflammatory reactions via Fn14 on HUVEC.
Harada
Norihiro
N
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Nakayama
Masafumi
M
Nakano
Hiroyasu
H
Fukuchi
Yoshinosuke
Y
Yagita
Hideo
H
Okumura
Ko
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D000074049:Cytokine TWEAK; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors
D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D018925:Chemokines; D000074049:Cytokine TWEAK; D019040:E-Selectin; D008565:Membrane Proteins; D016328:NF-kappa B; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D047992:TNF Receptor-Associated Factor 2; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; C000613299:Tnfrsf12a protein, mouse; C491645:Tnfsf12 protein, mouse; D048069:Tumor Necrosis Factors; D018799:Intercellular Adhesion Molecule-1