PMID- 26719146
OWN - NLM
STAT- MEDLINE
DCOM- 20160728
LR  - 20231213
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 310
IP  - 4
DP  - 2016 Feb 15
TI  - Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway 
      inflammation in mice.
PG  - L377-86
LID - 10.1152/ajplung.00174.2015 [doi]
AB  - Recent data indicate a role for airway epithelial necroptosis, a regulated form 
      of necrosis, and the associated release of damage-associated molecular patterns 
      (DAMPs) in the development of chronic obstructive pulmonary disease (COPD). DAMPs 
      can activate pattern recognition receptors (PRRs), triggering innate immune 
      responses. We hypothesized that cigarette smoke (CS)-induced epithelial 
      necroptosis and DAMP release initiate airway inflammation in COPD. Human 
      bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE), 
      and necrotic cell death (membrane integrity by propidium iodide staining) and 
      DAMP release (i.e., double-stranded DNA, high-mobility group box 1, heat shock 
      protein 70, mitochondrial DNA, ATP) were analyzed. Subsequently, BEAS-2B cells 
      were exposed to DAMP-containing supernatant of CS-induced necrotic cells, and the 
      release of proinflammatory mediators [C-X-C motif ligand 8 (CXCL-8), IL-6] was 
      evaluated. Furthermore, mice were exposed to CS in the presence and absence of 
      the necroptosis inhibitor necrostatin-1, and levels of DAMPs and inflammatory 
      cell numbers were determined in bronchoalveolar lavage fluid. CSE induced a 
      significant increase in the percentage of necrotic cells and DAMP release in 
      BEAS-2B cells. Stimulation of BEAS-2B cells with supernatant of CS-induced 
      necrotic cells induced a significant increase in the release of CXCL8 and IL-6, 
      in a myeloid differentiation primary response gene 88-dependent fashion. In mice, 
      exposure of CS increased the levels of DAMPs and numbers of neutrophils in 
      bronchoalveolar lavage fluid, which was statistically reduced upon treatment with 
      necrostatin-1. Together, we showed that CS exposure induces necrosis of bronchial 
      epithelial cells and subsequent DAMP release in vitro, inducing the production of 
      proinflammatory cytokines. In vivo, CS exposure induces neutrophilic airway 
      inflammation that is sensitive to necroptosis inhibition.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Pouwels, Simon D
AU  - Pouwels SD
AD  - Department of Pathology and Medical Biology, Experimental Pulmonology and 
      Inflammation Research, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands; GRIAC Research Institute, University 
      Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
FAU - Zijlstra, G Jan
AU  - Zijlstra GJ
AD  - Department of Pathology and Medical Biology, Experimental Pulmonology and 
      Inflammation Research, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands; GRIAC Research Institute, University 
      Medical Center Groningen, University of Groningen, Groningen, The Netherlands; 
      Department of Pulmonology, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands;
FAU - van der Toorn, Marco
AU  - van der Toorn M
AD  - Department of Pathology and Medical Biology, Experimental Pulmonology and 
      Inflammation Research, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands; GRIAC Research Institute, University 
      Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
FAU - Hesse, Laura
AU  - Hesse L
AD  - Department of Pathology and Medical Biology, Experimental Pulmonology and 
      Inflammation Research, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands; GRIAC Research Institute, University 
      Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
FAU - Gras, Renee
AU  - Gras R
AD  - Department of Pathology and Medical Biology, Experimental Pulmonology and 
      Inflammation Research, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands; GRIAC Research Institute, University 
      Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
FAU - Ten Hacken, Nick H T
AU  - Ten Hacken NH
AD  - GRIAC Research Institute, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands; Department of Pulmonology, University 
      Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
FAU - Krysko, Dmitri V
AU  - Krysko DV
AD  - Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 
      Ghent, Belgium; and Department of Biomedical Molecular Biology, Ghent University, 
      Ghent, Belgium.
FAU - Vandenabeele, Peter
AU  - Vandenabeele P
AD  - Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 
      Ghent, Belgium; and Department of Biomedical Molecular Biology, Ghent University, 
      Ghent, Belgium.
FAU - de Vries, Maaike
AU  - de Vries M
AD  - Department of Pathology and Medical Biology, Experimental Pulmonology and 
      Inflammation Research, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands; GRIAC Research Institute, University 
      Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
FAU - van Oosterhout, Antoon J M
AU  - van Oosterhout AJ
AD  - Department of Pathology and Medical Biology, Experimental Pulmonology and 
      Inflammation Research, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands; GRIAC Research Institute, University 
      Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
FAU - Heijink, Irene H
AU  - Heijink IH
AD  - Department of Pathology and Medical Biology, Experimental Pulmonology and 
      Inflammation Research, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands; GRIAC Research Institute, University 
      Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
FAU - Nawijn, Martijn C
AU  - Nawijn MC
AD  - Department of Pathology and Medical Biology, Experimental Pulmonology and 
      Inflammation Research, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands; GRIAC Research Institute, University 
      Medical Center Groningen, University of Groningen, Groningen, The Netherlands; 
      m.c.nawijn@umcg.nl.
LA  - eng
PT  - Journal Article
DEP - 20151230
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Smoke)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Epithelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - Lung/*metabolism
MH  - Mice
MH  - Necrosis/chemically induced
MH  - Neutrophils/*metabolism
MH  - Pulmonary Disease, Chronic Obstructive/etiology/metabolism
MH  - Smoke/*adverse effects
MH  - Smoking/adverse effects/metabolism
MH  - Nicotiana/*adverse effects
OTO - NOTNLM
OT  - airway epithelium
OT  - chronic obstructive pulmonary disease
OT  - cigarette smoke
OT  - damage-associated molecular patterns
OT  - necroptosis
EDAT- 2016/01/01 06:00
MHDA- 2016/07/29 06:00
CRDT- 2016/01/01 06:00
PHST- 2015/06/02 00:00 [received]
PHST- 2015/12/18 00:00 [accepted]
PHST- 2016/01/01 06:00 [entrez]
PHST- 2016/01/01 06:00 [pubmed]
PHST- 2016/07/29 06:00 [medline]
AID - ajplung.00174.2015 [pii]
AID - 10.1152/ajplung.00174.2015 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2016 Feb 15;310(4):L377-86. doi: 
      10.1152/ajplung.00174.2015. Epub 2015 Dec 30.