A comprehensive analysis of oxidative stress in the ozone-induced lung inflammation mouse model

In this study we investigated the acute and chronic effects of ozone exposure-induced oxidative stress related inflammation mechanics in mouse lung. In particular we investigated the oxidative stress-induced effects on HDAC2 modification and activation of the Nrf2 and HIF-1α signalling pathways. Male C57BL/6 mice were exposed to ozone (3 ppm) for 3 hours a day, 2 times a week for a period 1, 3 and 6 weeks. Control mice were exposed to normal air. After the last exposure mice were sacrificed for bronchoalveolar lavage (BAL) fluid and lung tissue collection. BAL total cell counts were elevated at all time points studied. This was associated with increased levels of chemokines and cytokines in all ozone exposed groups indicating the presence of a persistent inflammatory environment in the lung. Increased inflammation and Lm scores were observed in chronic exposed mice indicating emphysematous changes were present in lungs of chronic exposed mice. The anti-oxidative stress response was active (indicated by increased Nrf2 activity and protein) after 1 week of ozone exposure but this ability was lost after 3 and 6 weeks of ozone exposure. The transcription factor HIF-1α was elevated in 3 and 6 week ozone exposed mice and this was associated with increased gene expression levels of several of HIF-1α target genes including hdac2, vegf, keap1, and mif. HDAC2 protein was found to be phosphorylated and carbonylated in nuclear and cytoplasm fractions, respectively, a...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research