This is the first report to demonstrate that the internalization of exogenous Tbeta(4) is essential for its antiapoptotic activity in human corneal epithelial cells.

BACKGROUND:The mechanism between ventilator-induced lung injury (VILI) and multiple organ injury is unclear. The aim of our study was to investigate the mechanisms of VILI-induced distal organ injury. METHODS: VILI was induced in rat lungs with high tidal volume (V T ) ventilation of 40 mL/kg for 6 h. Rats with low V T ventilation of 6 mL/kg served as controls. Inflammatory and apoptotic indices in lung and distal organs were assessed. RESULTS: VILI increased lung weight, airway pressure, inflammation, and apoptotic pathologic changes without hemodynamic changes. The white blood cell count and the levels of H 2 O 2 , interleukin-1␤ (IL-1␤), tumor necrosis factor alpha, and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid were higher in the VILI group compared with the control group. H 2 O 2 , IL-1␤, and tumor necrosis factor alpha in blood from the left ventricle were up-regulated. H 2 O 2 , IL-1␤, tumor necrosis factor alpha, macrophage inflammatory protein-2, c-Jun N-terminal kinase, p38, nuclear factor kappa B, and caspase-3 in lung, heart, liver, and kidney tissues in the VILI group were up-regulated. Furthermore, the apoptotic score for the kidneys was higher than those for other distal organs in the VILI group. CONCLUSIONS: High V T ventilation induces VILI and is associated with inflammation and apoptosis in distal organs. Up-regulation of reactive oxygen species and cytokines in VILI is associated with systemic inflammatory responses. Kidney tissue appears to be more vulnerable than heart and liver tissues following VILI.

Apocynin (Apo) suppresses the generation of reactive oxygen species that are implicated in lipopolysaccharide (LPS)-induced lung injury (LPSLI). We thus hypothesized that Apo may attenuate LPSLI. In addition, we explored the cellular and molecular mechanisms of Apo treatment in LPSLI. Lipopolysaccharide-induced lung injury was induced by intratracheal instillation of 10 mg/kg LPS in isolated and perfused rat lung model. Apocynin was administered in the perfusate at 15 min before LPS was administered. Hemodynamics, lung injury indices, inflammatory responses, and activation of apoptotic pathways were assessed. There was an increase in lung vascular permeability associated with lung weight gain after LPS exposure. The levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), macrophage inflammatory protein 2, H2O2, and albumin increased in the bronchoalveolar lavage fluid. Adhesion molecule of neutrophil (CD31) was upregulated. The expression of TNF-α, IL-1β, glutathione, myeloperoxidase, JNK, P38, caspase 3, p-AKT, and plasminogen activator inhibitor 1 in lung tissue was greater in the LPS groups when compared with the control group. Upregulation and activation of nuclear factor κB occurred along with increased histopathologic lung injury score in LPSLI. The Apo attenuated these inflammatory responses including the levels of CD31, H2O2, TNF-α, IL-1β, myeloperoxidase, P38, and nuclear factor κB along with downregulation of apoptosis as reflected by caspase 3 and p-AKT. In addition, Apo attenuated the increase in lung weight, bronchoalveolar lavage fluid albumin content, and the histopathologic lung injury score. In conclusion, LPSLI is associated with increased inflammatory responses, apoptosis, and coagulation. The administration of Apo attenuates LPSLI through downregulation of the inflammatory responses and apoptosis.

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