Effect of steroid on hyperoxia-induced ICAM-1 expression in pulmonary endothelial cells.
Intercellular adhesion molecule-1 (ICAM-1) of the vascular endothelium plays a key role in the development of pulmonary oxygen toxicity. We studied the effect of steroid on hyperoxia-induced ICAM-1 expression using cultured endothelial cells in vitro. Human pulmonary artery endothelial cells (HPAECs) were cultured to confluence, and then the monolayers were exposed to either control (21% O(2)-5% CO(2)) or hyperoxic (90% O(2)-5% CO(2)) conditions with and without a synthetic glucocorticoid, methylprednisolone (MP). MP reduced hyperoxia-induced ICAM-1 and ICAM-1 mRNA expression in a dose-dependent manner. Neutrophil adhesion to hyperoxia-exposed endothelial cells was also inhibited by MP treatment. In addition, MP attenuated hyperoxia-induced H(2)O(2) production in HPAECs as assessed by flow cytometry. An electrophoretic mobility shift assay demonstrated that hyperoxia activated nuclear factor-kappaB (NF-kappaB) but not activator protein-1 (AP-1) and that MP attenuated hyperoxia-induced NF-kappaB activation dose dependently. With Western immunoblot analysis, IkappaB-alpha expression was decreased by hyperoxia and increased by MP treatment. These results suggest that MP downregulates hyperoxia-induced ICAM-1 expression by inhibiting NF-kappaB activation via increased IkappaB-alpha expression.
Suzuki
Y
Y
Department of Internal Medicine, Kitasato Institute Hospital, Tokyo 108-8642, Japan. suzukiyk@kitasato.or.jp
Nishio
K
K
Takeshita
K
K
Takeuchi
O
O
Watanabe
K
K
Sato
N
N
Naoki
K
K
Kudo
H
H
Aoki
T
T
Yamaguchi
K
K
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D018496:Hyperoxia / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008775:Methylprednisolone / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism
D005938:Glucocorticoids; D020672:I-kappa B Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D006861:Hydrogen Peroxide; D008775:Methylprednisolone