Objectives To explore ventilation induced cytokine production and the role of oxidant stress in lung stretch. Methods Both in vitro and in vivo models of ventilator-induced lung injury (VILI) were used. Alveolar epithelial cells were stretched in vitro to mimic the lung injury in VILI. Rats were ventilated at large tidal volume to produce ventilator-induced lung injury in vivo. A total of 23 inflammatory cytokines were screened with micro gene array in stretched alveolar epithelial cells. Cytokines found to have up-regulated in cells were measured in serum and lung tissue of rats exposed to large tidal volume ventilation. For investigating the intracellular pathway of cytokine up-regulation in VILI, exogenous TNF-α or H2O2 was added to culture media of alveolar epithelial cells. Cytokines were then measured. To explore the role of oxidant stress in VILI, N-acetylcysteine (NAC), as an anti-oxidant, was used in vitro and in vivo. Results We found that transforming growth factor-β1 (TGF-β1 and transforming growth factor-β2 (TGF β2) were up-regulated in stretched alveolar epithelial cells and also in serum of rats with large tidal volume ventilation. Tumor necrosis factor-α (TNF-α) had no effects on TGF-β production in alveolar epithelial cells. Exogenous H2O2, as an oxidant, increased TGF-β production in alveolar epithelial cells. NAC, an anti-oxidant, decreased stretch induced TGF-β production, along with a down-regulation of oxidant injury. NAC also blocked the up-regulation of TGF-β in in vivo model of VILI. Conclusion TGF-β1 and TGF-β2 were up-regulated in VILI. Oxidant injury mediated up-regulation of TGF-β in VILI. NAC, which attenuated oxidant injury and blocked TGF-β up-regulation in VILI, could be a future therapeutic strategy in VILI.

Objectives To explore ventilation induced cytokine production and the role of oxidant stress in lung stretch. Methods Both in vitro and in vivo models of ventilator-induced lung injury (VILI) were used. Alveolar epithelial cells were stretched in vitro to mimic the lung injury in VILI. Rats were ventilated at large tidal volume to produce ventilator-induced lung injury in vivo. A total of 23 inflammatory cytokines were screened with micro gene array in stretched alveolar epithelial cells. Cytokines found to have up-regulated in cells were measured in serum and lung tissue of rats exposed to large tidal volume ventilation. For investigating the intracellular pathway of cytokine up-regulation in VILI, exogenous TNF-? or H_ 2O_ 2 was added to culture media of alveolar epithelial cells. Cytokines were then measured. To explore the role of oxidant stress in VILI, N-acetylcysteine (NAC), as an anti-oxidant, was used in vitro and in vivo. Results We found that transforming growth factor-?_1 (TGF-?_1 and transforming growth factor-?_2 (TGF-?_2) were up-regulated in stretched alveolar epithelial cells and also in serum of rats with large tidal volume ventilation. Tumor necrosis factor-? (TNF-?) had no effects on TGF-? production in alveolar epithelial cells. Exogenous H_ 2O_ 2, as an oxidant, increased TGF-? production in alveolar epithelial cells. NAC, an anti-oxidant, decreased stretch induced TGF-? production, along with a down-regulation of oxidant injury. NAC also blocked the up-regulation of TGF-? in in vivo model of VILI. Conclusion TGF-?_1 and TGF-?_2 were up-regulated in VILI. Oxidant injury mediated up-regulation of TGF-? in VILI. NAC, which attenuated oxidant injury and blocked TGF-? up-regulation in VILI, could be a future therapeutic strategy in VILI.