OBJECTIVE: Ventilator-induced lung injury (VILI) is characterized by release of inflammatory cytokines, but the mechanisms are not well understood. We hypothesized that stretch-induced cytokine production is dependent on oxidant release and is regulated by intracellular glutathione (GSH) inhibition of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) binding. METHODOLOGY: Type 2-like alveolar epithelial cells (A549) were exposed to cyclic stretch at 15% strain for 4 h at 20 cycles/min with or without N-acetylcysteine (NAC) or glutathione monoethylester (GSH-e) to increase intracellular GSH, or buthionine sulfoximine (BSO), to deplete intracellular GSH. RESULTS: Cyclic stretch initially caused a decline in intracellular GSH and a rise in the levels of isoprostane, a marker of oxidant injury. This was followed by a significant increase in intracellular GSH and a decrease in isoprostane. Stretch-induced IL-8 and IL-6 production were significantly inhibited when intracellular GSH was further increased by NAC or GSH-e (P < 0.0001). Stretch-induced IL-8 and IL-6 production were augmented when intracellular GSH was depleted by BSO (P < 0.0001). NAC blocked stretch-induced NF-kappa B and AP-1 binding and inhibited IL-8 mRNA expression. CONCLUSIONS: We conclude that oxidant release may play a role in lung cell stretch-induced cytokine release, and antioxidants, which increase intracellular GSH, may protect lung cells against stretch-induced injury.
OBJECTIVE: Ventilator-induced lung injury (VILI) is characterized by release of inflammatory cytokines, but the mechanisms are not well understood. We hypothesized that stretch-induced cytokine production is dependent on oxidant release and is regulated by intracellular glutathione (GSH) inhibition of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) binding. METHODOLOGY: Type 2-like alveolar epithelial cells (A549) were exposed to cyclic stretch at 15% strain for 4 h at 20 cycles/min with or without N-acetylcysteine (NAC) or glutathione monoethylester (GSH-e) to increase intracellular GSH, or buthionine sulfoximine (BSO), to deplete intracellular GSH. RESULTS: Cyclic stretch initially caused a decline in intracellular GSH and a rise in the levels of isoprostane, a marker of oxidant injury. This was followed by a significant increase in intracellular GSH and a decrease in isoprostane. Stretch-induced IL-8 and IL-6 production were significantly inhibited when intracellular GSH was further increased by NAC or GSH-e (P < 0.0001). Stretch-induced IL-8 and IL-6 production were augmented when intracellular GSH was depleted by BSO (P < 0.0001). NAC blocked stretch-induced NF-kappa B and AP-1 binding and inhibited IL-8 mRNA expression. CONCLUSIONS: We conclude that oxidant release may play a role in lung cell stretch-induced cytokine release, and antioxidants, which increase intracellular GSH, may protect lung cells against stretch-induced injury.
Authors: Ozlem U Gurkan; Chaoxia He; Rachel Zielinski; Hamid Rabb; Landon S King; Jeffrey M Dodd-o; Franco R D'Alessio; Neil Aggarwal; David Pearse; Patrice M Becker Journal: Exp Lung Res Date: 2011-11-01 Impact factor: 2.459
Authors: Anna A Birukova; Panfeng Fu; Junjie Xing; Bakhtiyor Yakubov; Ivan Cokic; Konstantin G Birukov Journal: Am J Physiol Lung Cell Mol Physiol Date: 2010-03-26 Impact factor: 5.464
Authors: Rosanna Vaschetto; Jan W Kuiper; Shyh Ren Chiang; Jack J Haitsma; Jonathan W Juco; Stefan Uhlig; Frans B Plötz; Francesco Della Corte; Haibo Zhang; Arthur S Slutsky Journal: Anesthesiology Date: 2008-02 Impact factor: 7.892
Authors: Masahiro Hashizume; Marc Mouner; Joshua M Chouteau; Olena M Gorodnya; Mykhaylo V Ruchko; Barry J Potter; Glenn L Wilson; Mark N Gillespie; James C Parker Journal: Am J Physiol Lung Cell Mol Physiol Date: 2012-12-14 Impact factor: 5.464