Response of alveolar type II epithelial cells to mechanical stretch and lipopolysaccharide

Background: Although many therapeutic strategies have been developed clinically, the mortality associated with acute respiratory distress syndrome remains very high. Objectives: In this research, we used a cytomechanical method to elucidate the reason for this. Methods: A549 cells were stimulated with lipopolysaccharide (LPS; 1 or 100 ng/ml) and/or mechanical stretch ( 5, 15, 30%) in varying frequency (0.2, 0.5, 1 Hz) at indicated time (1, 2, 4 h). Real time PCR and enzyme-linked immunosorbent assay were used to measure mRNA and protein levels of IL-8. Results: In the presence of mechanical stretch, 100 ng/ml LPS significantly increased IL-8 production after 4 h of 5% stretch ( p < 0.05). In the presence of LPS, stretch enhanced LPS-induced IL-8 protein production in a force-, time- and frequency-dependent manner. At both the 1- and 4-hour time points, mechanical stretch and LPS increased IL-8 mRNA levels, respectively, and stretch enhanced LPS-induced IL-8 mRNA levels (p < 0.05). Conclusions: Using cytomechanic methods, we found a synergistic effect of LPS and mechanical stretch on IL-8 production. The response of alveolar type II cells to mechanical stretch depends on their different pathologic states and the applied mechanical stretch, which may reversely influence the outcome of patients with acute respiratory distress syndrome. Copyright (c) 2007 S. Karger AG, Basel.