Effect of diesel exhaust generated by a city bus engine on stress responses and innate immunity in primary bronchial epithelial cell cultures. (April 2018)

• Record Type: Journal Article
• Authors: Zarcone, M.C.; Duistermaat, E.; Alblas, M.J.; van Schadewijk, A.; Ninaber, D.K.; Clarijs, V.; Moerman, M.M.; Vaessen, D.; Hiemstra, P.S.; Kooter, I.M.
• Is Part Of: Toxicology in vitro. Volume 48(2018)
• Page Start: 221
• Page End: 231
• Publication Date: 2018-04
• Subjects: Human airway epithelium -- Diesel exhaust -- NTHi -- Antimicrobial response -- Integrated stress response -- Oxidative stress response; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2018.01.024
• Languages: English
• ISSNs: 0887-2333

Abstract

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: Emissions of an Euro V diesel city bus engine affect cultured human primary bronchial epithelial cells. Diesel emissions (DE) induce a transient oxidative stress response. DE inhibits the bacteria-induced expression of the antimicrobial peptide human beta-defensin-2 (DEFB4A). DE modulates the response to endoplasmic reticulum stress and the integrated stress response.