Stretchinduced IL-8 depends on c-Jun NH2-terminal and nuclear factor-Binducing kinases

pressure ventilation with large tidal volumes has been shown to cause release of cytokines, including interleukin (IL)-8. The mechanisms regulating lung stretch-induced cytokine production are unclear. We hypothesized that stretch-in-duced IL-8 production is dependent on the activation of the mitogen-activated protein kinases, c-Jun NH2-terminal ki-nases (JNK), p38, and/or extracellular signal-regulated ki-nase (ERK) 1/2. We exposed A549 cells, a type II-like alveolar epithelial cell line, to cyclic stretch at 20 cycles/min for 5 min–2 h. Cyclic stretch induced IL-8 protein production, IL-8 mRNA expression, and JNK activation, but only transient activation of p38 and ERK1/2. Inhibition of stretch-induced JNK activation by adenovirus-mediated gene transfer of stress-activated protein kinase (SEK-1), a dominant-nega-tive mutant of SEK-1, the immediate upstream activator o