Abstract
Harmful effects of diesel emissions can be investigated via exposures of human epithelial cells, but most of previous studies have largely focused on the use of diesel particles or emission sources that are poorly representative of engines used in current traffic.We studied the cellular response of primary bronchial epithelial cells (PBECs) at the air-liquid interface (ALI) to the exposure to whole diesel exhaust (DE) generated by a Euro V bus engine, followed by treatment with UV-inactivated non-typeable Haemophilus influenzae (NTHi) bacteria to mimic microbial exposure. The effect of prolonged exposures was investigated, as well as the difference in the responses of cells from COPD and control donors and the effect of emissions generated during a cold start. HMOX1 and NQO1 expression was transiently induced after DE exposure. DE inhibited the NTHi-induced expression of human beta-defensin-2 (DEFB4A) and of the chaperone HSPA5/BiP. In contrast, expression of the stress-induced PPP1R15A/GADD34 and the chemokine CXCL8 was increased in cells exposed to DE and NTHi. HMOX1 induction was significant in both COPD and controls, while inhibition of DEFB4A expression by DE was significant only in COPD cells. No significant differences were observed when comparing cellular responses to cold engine start and prewarmed engine emissions.
Highlights
Diesel exhaust (DE) exposures constitute a health risk for large populations living in urbanized areas (Laumbach and Kipen, 2012; Schmidt, 2016)
Similar effects of epithelial cell cultures, as shown by its ability to decrease induced human beta defensin (hBD)-2 expression (Zarcone et al, 2017). Another mechanism that may deregulate epithelial defense in chronic obstructive pulmonary disease (COPD) is provided by the observation of chronic activation of the integrated stress response (ISR) in COPD and other inflammatory lung diseases that may result from oxidants such as cigarette smoke as well as micro-organisms (Steiling et al, 2013; van 't Wout et al, 2014)
Inflammatory (CXCL8) and integrated stress (PPP1R15A/GADD34) responses were activated in cells exposed to diesel exhaust (DE) and treated with non-typeable Haemophilus influenzae (NTHi), while DE caused an inhibition of the NTHi-induced expression of the chaperone protein BiP (HSPA5)
Summary
Diesel exhaust (DE) exposures constitute a health risk for large populations living in urbanized areas (Laumbach and Kipen, 2012; Schmidt, 2016). The lung epithelium releases antimicrobial peptides and proteins such as human beta defensin (hBD)-2 and S100 calcium binding protein (S100A7) in response to bacterial infections (Hiemstra et al, 2015) Impairment of such defenses by cigarette smoke was demonstrated and implicated in the increased susceptibility of smokers to respiratory infection (Herr et al, 2009; Pace et al, 2012). We have recently obtained evidence that DE may exert similar effects of epithelial cell cultures, as shown by its ability to decrease induced hBD-2 expression (Zarcone et al, 2017) Another mechanism that may deregulate epithelial defense in COPD is provided by the observation of chronic activation of the integrated stress response (ISR) in COPD and other inflammatory lung diseases that may result from oxidants such as cigarette smoke as well as micro-organisms (Steiling et al, 2013; van 't Wout et al, 2014). Detrimental effects of chronic activation of the ISR may contribute to the effects of DE
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