Effects of soluble epoxide hydrolase inhibitor on inflammatory cytokine release and gene expression of bronchial epithelial cells from patients with COPD

Chronic obstructive pulmonary disease (COPD) is associated with chronic airway inflammation that is resistant to steroids and current anti-inflammatory treatments. Recent studies suggest that soluble epoxide hydrolase inhibitors (sEHI) may reduce airway inflammation in animal models of COPD. However, it is not clear whether these agents show the same effect on human airway epithelial cells. The aim of the present study was to investigate effects of sEHI on primary bronchial epithelial cell (BEC) viability, release of inflammatory cytokines and gene expression in these cells. We cultured primary BECs from non-smokers, smokers and patients with COPD, and incubated these with 0.1,1,10 and 33µM sEHI for 24 hours in the absence and presence of 1ng/ml of interleukin (IL)-1β. Cell culture supernatants were analysed for granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-8, whereas BEC viability was determined by MTT assay. Higher concentrations of sEHI (10µM and 33µM) significantly (p<0.0001) decreased the viability of non-smoker cells compared to control cells treated with 0µM sEHI. Similarly, both 10µM (p<0.01) and 33µM (p<0.001) sEHI decreased the viability of COPD cells. However, sEHI did not affect viability of BECs from smokers. sEHI did not affect the release and mRNA expression for GM-CSF or IL-8 in primary BECs, either. When study groups compared, cytokine release from COPD cells, both with and without incubation with sEHI, was greater than other cell groups. In conclusion, our findings demonstrate that the higher concentrations of sEHI can decrease the viability of BEC without changing cytokine release, gene expression and that their effect in COPD inflammation is limited.