Stretch of Septic Monolayers Figure 3. Expression of tight junction proteins following 60 minutes of stretch. Tight junction protein expression in sham (&) and 2CLP (%) with and without stretch. *significantly different from sham, bar indicates significantly different between sham and 2CLP, p,0.05 (mean 6 SE, N$3 isolations). doi:10.1371/journal.pone.0038748.g003 Discussion Ventilation of septic patients is necessary to maintain proper blood gas levels; however, the combination of sepsis and ventilation often leads to the development of acute lung injury (ALI) [2]. A symptom of ALI is the breakdown in epithelial barrier function, which results in edema formation in the airspaces of the lung [25]. We previously demonstrated that stretch to a high magnitude (100% TLC) increases monolayer permeability and activates JNK, ERK, and p38 MAPk in healthy cells, and that inhibition of JNK and ERK reduces the stretch-induced perme- ability increases [16]. Furthermore, we have developed a model of an epithelium formed by cells from a septic environment and demonstrated that even without stretch these monolayers are less restrictive to paracellular ion flux and have increased phosphor- ylation of JNK and ERK MAPk [15]. Inhibition of ERK, not JNK, increases monolayer resistance to ion flux in these unstretched septic monolayers. We hypothesized that since sepsis and mechanical ventilation independently activate a common signaling pathway (MAPk) which affects epithelial permeability, PLoS ONE | www.plosone.org 5 June 2012 | Volume 7 | Issue 6 | e38748