Effect of diesel exhaust (DE) on stress responses and innate immunity in primary bronchial epithelial cell (PBEC) cultures from patients with COPD and controls

Exposure to diesel emissions is associated with adverse effects on respiratory health, especially in COPD and asthma. We developed an in vitro model to better understand these adverse health effects, using differentiated human PBEC that are exposed to whole DE at the air-liquid interface (ALI). The aim of this study was to evaluate the effect of DE generated by a typical Euro V truck engine with after-treatment device, using PBEC from (ex)-smoking COPD and non-COPD patients. ALI-PBEC from 5 non-COPD donors were exposed to DE for 6 h, causing a significant increase in mRNA levels of HMOX1 (5-fold) and NQO1 (1.5-fold) (oxidative stress response). DE also significantly increased the ability of Haemophilus influenzae (NTHi) to increase the marker of the response to endoplasmic reticulum stress, PPP1R15A / GADD34 (3-fold), as well as causing a non-significant increase in CXCL8 mRNA. Next, effects of shorter (2.5h) exposures were assessed using cells from COPD (n=7) and non-COPD (n=5) patients. DE increased HMOX1 mRNA (2.5-fold), which reached statistical significance only in COPD patients. Furthermore, DE caused a 40% decrease in the ability of NTHi to increase expression of the antimicrobial peptide DEFB4A , reaching significance in cells from the COPD patients. Our results demonstrate that PBEC respond to exposure to DE derived from a typical Euro V truck engine. The results indicate that DE may impair the host defence function of the airway epithelium, and provide preliminary evidence that this response may be more pronounced in cultures from COPD patients. Supported by a grant from the Lung Foundation Netherlands (#3.2.11.009).