Mechanical stress upregulates intercellular adhesion molecule-1 in pulmonary epithelial cells.

摘要

BACKGROUND: Mechanical ventilation can affect the lung, causing edema and alveolar inflammation. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in this inflammatory response. OBJECTIVE: The aims of this study were to investigate whether cyclic cell stretch upregulates the production of ICAM-1 by human alveolar epithelium and to explore possible mechanisms of upregulation. METHODS: Human type 2-like alveolar epithelial cells (A549 cells) were exposed to cyclic tensile strain via a four-point bending system, with strains of varying frequency (0.2, 0.5, and 1 Hz), duration (0, 1, 3, and 6 h), and magnitude (500, 1,000, and 2,000 microstrain). Strain was applied at varying frequency (0.2, 0.5, 1 Hz) but at constant time (3 h) and magnitude (1,000 microstrain), at varying duration (0, 1, 3, and 6 h) but at constant frequency (0.5 Hz) and magnitude (1,000 microstrain), or at varying magnitude (500, 1,000, and 2,000 microstrain) but at constant time (3 h) and frequency (0.5 Hz). RESULTS: Mechanical loading induced ICAM-1 protein and mRNA production in a frequency- and duration-dependent manner. At the 3-hour time point, large loadings (1,000 or 2,000 microstrain) upregulated ICAM-1 protein production, but there was no statistically significant difference between these two groups (p > 0.05). PD98059, a specific inhibitor of extracellular signal-regulated kinase (ERK), and N-acetylcysteine (NAC), an antioxidant, partially abrogated the stretch-induced ICAM-1 protein upregulation at the 3-hour loading. CONCLUSION: Mechanical strain can upregulate ICAM-1 production. The response is frequency and duration dependent, which may involve both ERK pathways and reactive oxidant species production.