title: Anti-TNF-alpha antibody (infliximab) therapy supports the recovery of eNOS and VEGFR2 protein expression in endothelial cells.
abstract: The aim of this study is to investigate the effect of sera obtained from patients of Crohn's disease treated by anti-TNF-alpha antibody (Infliximab) on the expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor receptor-2 (VEGFR2) protein in human umbilical vein endothelial cells (HUVEC) cultured in vitro. HUVEC was cultured in the presence of sera derived from patients before and after treatment, or from healthy individuals. Effects of sera on the expression of eNOS and VEGFR2 were monitored by determination of mRNA and protein levels using real time quantitative PCR and Western blot analysis, respectively. The serum of Crohn's patients contained elevated levels of TNF-alpha (34±1.80 pg/mL), which resulted in a decrease in the protein level of eNOS in HUVEC with a simultaneous induction of VEGFR2. Infliximab treatment normalized the expression level of these proteins by decreasing TNF-alpha level, particularly in those cases when clinical healing was also recorded, and it also conferred restitution of the level of angiogenic cytokines. Results suggest that altered angiogenesis possibly contributes to the initiation and perpetuation of inflammatory processes in inflammatory bowel disease (IBD). Endothelial dysfunction, a selective feature of Crohn's disease is beneficially affected by intravascular TNF-alpha neutralization.
authors.affiliation: 2nd Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Altorjay
authors.forename: Z
authors.initials: Z
authors.lastname: Veréb
authors.forename: Z
authors.initials: Z
authors.lastname: Serfozo
authors.forename: I
authors.initials: I
authors.lastname: Bacskai
authors.forename: R
authors.initials: R
authors.lastname: Bátori
authors.forename: F
authors.initials: F
authors.lastname: Erdodi
authors.forename: M
authors.initials: M
authors.lastname: Udvardy
authors.forename: S
authors.initials: S
authors.lastname: Sipka
authors.forename: Á
authors.initials: Á
authors.lastname: Lányi
authors.forename: É
authors.initials: É
authors.lastname: Rajnavölgyi
authors.forename: K
authors.initials: K
authors.lastname: Palatka
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D042783:Endothelial Cells / Q000201:enzymology* / Q000276:immunology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D000069285:Infliximab; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000069285:Infliximab; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D040301:Vascular Endothelial Growth Factor Receptor-2; C046366:angiogenin; D012259:Ribonuclease, Pancreatic