Nitric oxide attenuates vascular endothelial cadherin-mediated vascular integrity in human chronic inflammation.
In this study, we examined the role of nitric oxide (NO) in controlling vascular integrity mediated by vascular endothelial (VE)-cadherin in chronic inflammation. Periapical granulomas were analysed for the expression of inducible NO synthase (iNOS) and VE-cadherin, and more iNOS expression than VE-cadherin was shown. Human umbilical vein endothelial cells (HUVECs) were stimulated with proinflammatory cytokines and lipopolysaccharide extracted from Porphyromonas gingivalis and it induced iNOS expression, whereas it reduced VE-cadherin expression, compared with negative controls. On the other hand, pre-incubation with 1400W, an iNOS-specific inhibitor, markedly reduced iNOS expression in stimulated HUVECs and restored VE-cadherin expression to its control level, suggesting that vascular integrity was modulated in conjunction with the reduction of NO. Immunocytochemistry confirmed the functional role of NO in cultured HUVEC monolayers with or without 1400W. These data are consistent with a hypothesis suggesting that NO could attenuate VE-cadherin-mediated vascular integrity in human chronic inflammation.
Hama
S
S
Department of Endodontics, Nihon University School of Dentistry, Tokyo, Japan.
Takeichi
O
O
Fujisaki
K
K
Tanabe
N
N
Maeno
M
M
Ochiai
K
K
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010484:Periapical Granuloma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D055815:Young Adult; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D016207:Cytokines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; D000099152:Cadherin 5