Diesel exhaust alters the response of cultured primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD) to non-typeable Haemophilus influenzae

Respiratory Research

Research

Pieter S. Hiemstra¹  Maria C. Zarcone¹  Annemarie van Schadewijk¹  Ingeborg M. Kooter²  Evert Duistermaat³ 

[1] Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands;Netherlands Organization for Applied Scientific Research, Utrecht, The Netherlands;Triskelion BV, Zeist, The Netherlands;

关键词: Airway epithelial cells;    Diesel exhaust;    Air pollution;    COPD;    Haemophilus influenzae;    Integrated stress response;    Antimicrobial response;    Antimicrobial peptides;   

DOI  :  10.1186/s12931-017-0510-4

 received in 2016-06-14, accepted in 2017-01-16,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundExacerbations constitute a major cause of morbidity and mortality in patients suffering from chronic obstructive pulmonary disease (COPD). Both bacterial infections, such as those with non-typeable Haemophilus influenzae (NTHi), and exposures to diesel engine emissions are known to contribute to exacerbations in COPD patients. However, the effect of diesel exhaust (DE) exposure on the epithelial response to microbial stimulation is incompletely understood, and possible differences in the response to DE of epithelial cells from COPD patients and controls have not been studied.MethodsPrimary bronchial epithelial cells (PBEC) were obtained from age-matched COPD patients (n = 7) and controls (n = 5). PBEC were cultured at the air-liquid interface (ALI) to achieve mucociliary differentiation. ALI-PBECs were apically exposed for 1 h to a stream of freshly generated whole DE or air. Exposure was followed by 3 h incubation in presence or absence of UV-inactivated NTHi before analysis of epithelial gene expression.ResultsDE alone induced an increase in markers of oxidative stress (HMOX1, 50–100-fold) and of the integrated stress response (CHOP, 1.5–2-fold and GADD34, 1.5-fold) in cells from both COPD patients and controls. Exposure of COPD cultures to DE followed by NTHi caused an additive increase in GADD34 expression (up to 3-fold). Importantly, DE caused an inhibition of the NTHi-induced expression of the antimicrobial peptide S100A7, and of the chaperone protein HSP5A/BiP.ConclusionsOur findings show that DE exposure of differentiated primary airway epithelial cells causes activation of the gene expression of HMOX1 and markers of integrated stress response to a similar extent in cells from COPD donors and controls. Furthermore, DE further increased the NTHi-induced expression of GADD34, indicating a possible enhancement of the integrated stress response. DE reduced the NTHi-induced expression of S100A7. These data suggest that DE exposure may cause adverse health effects in part by decreasing host defense against infection and by modulating stress responses.

【 授权许可】

CC BY   
© The Author(s). 2017