Exogenous interleukin-10 attenuates hyperoxia-induced acute lung injury in mice.

NEW FINDINGS: What is the central question of this study? It is not known whether treatment with interleukin-10 (IL-10) attenuates hyperoxia-induced acute lung injury in mice. What is the main finding and its importance? Our results showed that exogenous IL-10 treatment alleviated hyperoxia-induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases. Lung injury caused by breathing air enriched with oxygen continues to be a major problem in clinical medicine. Here, we investigated the therapeutic role of interleukin-10 (IL-10) in hyperoxia-induced acute lung injury in mice. In the first experiment, mice were exposed to room air or 95% O2 and treated with IL-10 simultaneously. In the second experiment, wild-type mice and IL-10(-/-) mice were exposed to room air or 95% O2 . Exogenous IL-10 treatment attenuated hyperoxia-induced acute lung injury, evidenced by a reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, cell numbers and protein content in bronchoalveolar lavage fluid and cell death. Interleukin-10 treatment markedly prolonged the survival of mice during oxygen exposure. Interleukin-10 treatment reduced the activity of myeloperoxidase and mRNA levels of interleukin-6, tumour necrosis factor-α and macrophage inflammatory protein 2, suppressed nuclear factor-κB activation and decreased inducible nitric oxide synthnase expression and nitric oxide formation in lungs of mice exposed to hyperoxia. Interleukin-10 treatment suppressed activities of matrix metalloproteinase 2 and matrix metalloproteinase 9 and reduced lung permeability in mice during oxygen exposure. Furthermore, absence of IL-10 aggravated hyperoxia-induced acute lung injury and reduced the duration of survival of mice during oxygen exposure, which was attenuated by treatment with IL-10. In conclusion, our results show that exogenous IL-10 treatment alleviates hyperoxia-induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases. This suggests that IL-10 treatment may be a promising therapeutic strategy to reduce lung injury in patients exposed to hyperoxia.

Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells.

The bone protective effects of the hydrogen molecule (H2) have been demonstrated in several osteoporosis models while the underlying molecular mechanism has remained unclear. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. In this work, we evaluated the effects of incubation with H2 on receptor activator of NFκB ligand (RANKL)-induced osteoclast differentiation. We found that treatment with H2 prevented RANKL-induced osteoclast differentiation in RAW264.7 cells and BMMs. Treatment with H2 inhibits the ability to form resorption pits of BMMs stimulated by RANKL. Treatment with H2 reduced mRNA levels of osteoclast-specific markers including tartrate resistant acid phosphatase, calcitonin receptor, cathepsin K, metalloproteinase-9, carbonic anhydrase typeII, and vacuolar-type H(+)-ATPase. Treatment with H2 decreased intracellular reactive oxygen species (ROS) formation, suppressed NADPH oxidase activity, down-regulated Rac1 activity and Nox1 expression, reduced mitochondrial ROS formation, and enhanced nuclear factor E2-related factor 2 nuclear translocation and heme oxygenase-1 activity. In addition, treatment with H2 suppressed RANKL-induced expression of nuclear factor of activated T cells c1 and c-Fos. Furthermore, treatment with H2 suppressed NF-κB activation and reduced phosphorylation of p38, extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and protein kinases B (AKT) stimulated with RANKL. In conclusion, hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-κB, mitogen-activated protein kinase and AKT pathways.

Treatment with exogenous hydrogen sulfide attenuates hyperoxia-induced acute lung injury in mice.

The aim of this work was to test the effect of treatment with hydrogen sulfide (H2S) on hyperoxia-induced acute lung injury in mice. Mice were exposed to room air or 95 % O2, and treated with NaHS (intraperitoneal injection of 0.1 ml/kg/day of 0.56 mol/l NaHS). Treatment with H2S partly restored the reduced H2S levels in plasma and lungs of mice exposed to hyperoxia. Treatment with H2S attenuated hyperoxia-induced acute lung injury marked by reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, and cell numbers and protein content in bronchoalveolar lavage (BAL) and decreased apoptosis. Treatment with H2S markedly prolonged the survival of mice under oxygen exposure. Treatment with H2S abated hyperoxia-induced oxidative stress marked by reduced malondialdehyde and peroxynitrite formation, reduced NADPH oxidase activity, enhanced translocation of nuclear factor E2-related factor (Nrf2) into nucleus and increased activity of HO-1. Treatment with H2S decreased IL-1ß, MCP-1, and MIP-2, and increased IL-10 expression in lungs of mice exposed to hyperoxia. Treatment with H2S decreased NFκB activity and iNOS expression in lungs, and reduced NOx content in BAL of mice exposed to hyperoxia. Treatment with H2S reduced lung permeability and suppressed VEGF release and VEGFR2 expression in lungs of mice under oxygen exposure. Treatment with exogenous H2S attenuated hyperoxia-induced acute lung injury through abating oxidative stress, suppressing inflammation, and reducing lung permeability in mice.