Effects of cigarette smoke extract on human airway smooth muscle cells in COPD

Ling Chen; Qi Ge; Gavin Tjin; Hatem Alkhouri; Linghong Deng; Corry-Anke Brandsma; Ian Adcock; Wim Timens; Dirkje Postma; Janette K Burgess; Judith L Black; Brian G G Oliver

doi:10.1183/09031936.00171313

Effects of cigarette smoke extract on human airway smooth muscle cells in COPD

Eur Respir J. 2014 Sep;44(3):634-46. doi: 10.1183/09031936.00171313. Epub 2014 Jun 25.

Authors

Ling Chen¹, Qi Ge², Gavin Tjin³, Hatem Alkhouri⁴, Linghong Deng⁵, Corry-Anke Brandsma⁶, Ian Adcock⁷, Wim Timens⁶, Dirkje Postma⁸, Janette K Burgess⁹, Judith L Black², Brian G G Oliver¹⁰

Affiliations

¹ Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Shapingba, Chongqing, China Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia.
² Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia.
³ Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia Central Clinical School, The University of Sydney, Sydney, NSW, Australia.
⁴ Respiratory Research Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia.
⁵ Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Shapingba, Chongqing, China Institute of Biomedical Engineering and Health Science, Changzhou University, Changzhou, Jiangsu, China.
⁶ Dept of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁷ Thoracic Medicine, Imperial College London, National Heart and Lung Institute, London, UK.
⁸ Dept of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁹ Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia Discipline of Pharmacology, The University of Sydney, Sydney, NSW, Australia Central Clinical School, The University of Sydney, Sydney, NSW, Australia.
¹⁰ Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, NSW, Australia brian.oliver@uts.edu.au.

PMID: 24969654
DOI: 10.1183/09031936.00171313

Abstract

We hypothesised that the response to cigarette smoke in airway smooth muscle (ASM) cells from smokers with chronic obstructive pulmonary disease (COPD) would be intrinsically different from smokers without COPD, producing greater pro-inflammatory mediators and factors relating to airway remodelling. ASM cells were obtained from smokers with or without COPD, and then stimulated with cigarette smoke extract (CSE) or transforming growth factor-β1. The production of chemokines and matrix metalloproteinases (MMPs) were measured by ELISA, and the deposition of collagens by extracellular matrix ELISA. The effects of CSE on cell attachment and wound healing were measured by toluidine blue attachment and cell tracker green wound healing assays. CSE increased the release of CXCL8 and CXCL1 from human ASM cells, and cells from smokers with COPD produced more CSE-induced CXCL1. The production of MMP-1, -3 and -10, and the deposition of collagen VIII alpha 1 (COL8A1) were increased by CSE, especially in the COPD group which had higher production of MMP-1 and deposition of COL8A1. CSE decreased ASM cell attachment and wound healing in the COPD group only. ASM cells from smokers with COPD were more sensitive to CSE stimulation, which may explain, in part, why some smokers develop COPD.

©ERS 2014.

MeSH terms

Airway Remodeling
Bronchi / drug effects*
Cell Line
Cell Movement
Cell Survival
Collagen Type VIII / metabolism
Enzyme-Linked Immunosorbent Assay
Extracellular Matrix / metabolism
Fluoresceins / chemistry
Humans
Immunohistochemistry
Inflammation
Matrix Metalloproteinase 1 / metabolism
Matrix Metalloproteinases / metabolism
Myocytes, Smooth Muscle / drug effects*
Nicotiana / adverse effects
Pulmonary Disease, Chronic Obstructive / etiology*
Pulmonary Disease, Chronic Obstructive / physiopathology
Real-Time Polymerase Chain Reaction
Respiratory System / drug effects
Smoking / adverse effects*
Tolonium Chloride / chemistry
Transcription Factor AP-1 / metabolism
Transforming Growth Factor beta1 / metabolism
Wound Healing

Substances

Collagen Type VIII
Fluoresceins
Transcription Factor AP-1
Transforming Growth Factor beta1
5-chloromethylfluorescein
Tolonium Chloride
Matrix Metalloproteinases
Matrix Metalloproteinase 1