Publication

Cigarette smoke exposure decreases CFLAR expression in the bronchial epithelium, augmenting susceptibility for lung epithelial cell death and DAMP release

Faiz, A., Heijink, I. H., Vermeulen, C. J., Guryev, V., van den Berge, M., Nawijn, M. C. & Pouwels, S. D., 20-Aug-2018, In : Scientific Reports. 8, 1, 9 p., 12426.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Faiz, A., Heijink, I. H., Vermeulen, C. J., Guryev, V., van den Berge, M., Nawijn, M. C., & Pouwels, S. D. (2018). Cigarette smoke exposure decreases CFLAR expression in the bronchial epithelium, augmenting susceptibility for lung epithelial cell death and DAMP release. Scientific Reports, 8(1), [12426]. https://doi.org/10.1038/s41598-018-30602-7

Author

Faiz, Alen ; Heijink, Irene H ; Vermeulen, Cornelis J ; Guryev, Victor ; van den Berge, Maarten ; Nawijn, Martijn C ; Pouwels, Simon D. / Cigarette smoke exposure decreases CFLAR expression in the bronchial epithelium, augmenting susceptibility for lung epithelial cell death and DAMP release. In: Scientific Reports. 2018 ; Vol. 8, No. 1.

Harvard

Faiz, A, Heijink, IH, Vermeulen, CJ, Guryev, V, van den Berge, M, Nawijn, MC & Pouwels, SD 2018, 'Cigarette smoke exposure decreases CFLAR expression in the bronchial epithelium, augmenting susceptibility for lung epithelial cell death and DAMP release', Scientific Reports, vol. 8, no. 1, 12426. https://doi.org/10.1038/s41598-018-30602-7

Standard

Cigarette smoke exposure decreases CFLAR expression in the bronchial epithelium, augmenting susceptibility for lung epithelial cell death and DAMP release. / Faiz, Alen; Heijink, Irene H; Vermeulen, Cornelis J; Guryev, Victor; van den Berge, Maarten; Nawijn, Martijn C; Pouwels, Simon D.

In: Scientific Reports, Vol. 8, No. 1, 12426, 20.08.2018.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Faiz A, Heijink IH, Vermeulen CJ, Guryev V, van den Berge M, Nawijn MC et al. Cigarette smoke exposure decreases CFLAR expression in the bronchial epithelium, augmenting susceptibility for lung epithelial cell death and DAMP release. Scientific Reports. 2018 Aug 20;8(1). 12426. https://doi.org/10.1038/s41598-018-30602-7


BibTeX

@article{5d527219e9de484789ca0c45e8003d8e,
title = "Cigarette smoke exposure decreases CFLAR expression in the bronchial epithelium, augmenting susceptibility for lung epithelial cell death and DAMP release",
abstract = "Cigarette smoking is a major risk factor for the inflammatory disease, chronic obstructive pulmonary disease (COPD). The mechanism by which cigarette smoke (CS) induces chronic lung inflammation is still largely unknown. We hypothesize that immunogenic airway epithelial cell death is involved in the initiation of the inflammatory response. We previously identified CFLAR, the gene encoding the cell death regulator protein c-FLIP, to be associated with CS-induced release of damage-associated molecular patterns (DAMPs). Here, we investigated the effect of CS on expression levels of CFLAR in bronchial biopsies from smokers and non-smokers and CFLAR transcript isoform-expression in a data-set of air-liquid interface-differentiated bronchial epithelial cells. Furthermore, CFLAR was down-regulated by siRNA in lung epithelial A549 cells, followed by investigation of the effects on apoptosis, necrosis and DAMP release. CS exposure significantly decreased CFLAR expression in bronchial epithelial cells. Moreover, we observed a shift in relative abundance of the isoforms c-FLIPS and c-FLIPL transcripts in bronchial biopsies of current smokers compared to non-smokers, consistent with a shift towards necroptosis. In vitro, down-regulation of CFLAR increased apoptosis at baseline as well as CS extract-induced necrosis and DAMP release. In conclusion, CS exposure decreases CFLAR expression, which might increase susceptibility to immunogenic cell death.",
keywords = "OBSTRUCTIVE PULMONARY-DISEASE, AIRWAY INFLAMMATION, COPD, NECROPTOSIS, ACTIVATION, APOPTOSIS, PROTEIN, CFLIP, FLIP, MICE",
author = "Alen Faiz and Heijink, {Irene H} and Vermeulen, {Cornelis J} and Victor Guryev and {van den Berge}, Maarten and Nawijn, {Martijn C} and Pouwels, {Simon D}",
year = "2018",
month = aug,
day = "20",
doi = "10.1038/s41598-018-30602-7",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Cigarette smoke exposure decreases CFLAR expression in the bronchial epithelium, augmenting susceptibility for lung epithelial cell death and DAMP release

AU - Faiz, Alen

AU - Heijink, Irene H

AU - Vermeulen, Cornelis J

AU - Guryev, Victor

AU - van den Berge, Maarten

AU - Nawijn, Martijn C

AU - Pouwels, Simon D

PY - 2018/8/20

Y1 - 2018/8/20

N2 - Cigarette smoking is a major risk factor for the inflammatory disease, chronic obstructive pulmonary disease (COPD). The mechanism by which cigarette smoke (CS) induces chronic lung inflammation is still largely unknown. We hypothesize that immunogenic airway epithelial cell death is involved in the initiation of the inflammatory response. We previously identified CFLAR, the gene encoding the cell death regulator protein c-FLIP, to be associated with CS-induced release of damage-associated molecular patterns (DAMPs). Here, we investigated the effect of CS on expression levels of CFLAR in bronchial biopsies from smokers and non-smokers and CFLAR transcript isoform-expression in a data-set of air-liquid interface-differentiated bronchial epithelial cells. Furthermore, CFLAR was down-regulated by siRNA in lung epithelial A549 cells, followed by investigation of the effects on apoptosis, necrosis and DAMP release. CS exposure significantly decreased CFLAR expression in bronchial epithelial cells. Moreover, we observed a shift in relative abundance of the isoforms c-FLIPS and c-FLIPL transcripts in bronchial biopsies of current smokers compared to non-smokers, consistent with a shift towards necroptosis. In vitro, down-regulation of CFLAR increased apoptosis at baseline as well as CS extract-induced necrosis and DAMP release. In conclusion, CS exposure decreases CFLAR expression, which might increase susceptibility to immunogenic cell death.

AB - Cigarette smoking is a major risk factor for the inflammatory disease, chronic obstructive pulmonary disease (COPD). The mechanism by which cigarette smoke (CS) induces chronic lung inflammation is still largely unknown. We hypothesize that immunogenic airway epithelial cell death is involved in the initiation of the inflammatory response. We previously identified CFLAR, the gene encoding the cell death regulator protein c-FLIP, to be associated with CS-induced release of damage-associated molecular patterns (DAMPs). Here, we investigated the effect of CS on expression levels of CFLAR in bronchial biopsies from smokers and non-smokers and CFLAR transcript isoform-expression in a data-set of air-liquid interface-differentiated bronchial epithelial cells. Furthermore, CFLAR was down-regulated by siRNA in lung epithelial A549 cells, followed by investigation of the effects on apoptosis, necrosis and DAMP release. CS exposure significantly decreased CFLAR expression in bronchial epithelial cells. Moreover, we observed a shift in relative abundance of the isoforms c-FLIPS and c-FLIPL transcripts in bronchial biopsies of current smokers compared to non-smokers, consistent with a shift towards necroptosis. In vitro, down-regulation of CFLAR increased apoptosis at baseline as well as CS extract-induced necrosis and DAMP release. In conclusion, CS exposure decreases CFLAR expression, which might increase susceptibility to immunogenic cell death.

KW - OBSTRUCTIVE PULMONARY-DISEASE

KW - AIRWAY INFLAMMATION

KW - COPD

KW - NECROPTOSIS

KW - ACTIVATION

KW - APOPTOSIS

KW - PROTEIN

KW - CFLIP

KW - FLIP

KW - MICE

U2 - 10.1038/s41598-018-30602-7

DO - 10.1038/s41598-018-30602-7

M3 - Article

C2 - 30127367

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 12426

ER -

ID: 64752144