ALUNG February 22/2

Suzuki, Yukio, Kazumi Nishio, Kei Takeshita, Osamu Takeuchi, Kenji Watanabe, Nagato Sato, Katsuhiko Naoki, Hiroyasu Kudo, Takuya Aoki, and Kazuhiro Yamaguchi. Effect of steroid on hyperoxia-induced ICAM-1 expression in pulmonary endothelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 278: L245–L252, 2000.—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% O2-5% CO2) or hyperoxic (90% O2-5% CO2) conditions with and without a synthetic glucocorticoid, methylprednisolone (MP). MP reduced hyperoxiainduced ICAM-1 and ICAM-1 mRNA expression in a dosedependent manner. Neutrophil adhesion to hyperoxiaexposed endothelial cells was also inhibited by MP treatment. In addition, MP attenuated hyperoxia-induced H2O2 production in HPAECs as assessed by flow cytometry. An electrophoretic mobility shift assay demonstrated that hyperoxia activated nuclear factor-kB (NF-kB) but not activator protein-1 (AP-1) and that MP attenuated hyperoxia-induced NF-kB activation dose dependently. With Western immunoblot analysis, IkB-a expression was decreased by hyperoxia and increased by MP treatment. These results suggest that MP downregulates hyperoxia-induced ICAM-1 expression by inhibiting NF-kB activation via increased IkB-a expression.