Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers

Identification of biomarkers of cigarette smoke -induced lung damage and early COPD is an area of intense interest. Glucose regulated protein of 78 kD (i.e., GRP78), a multi-functional protein which mediates cell responses to oxidant stress, is increased in the lungs of cigarette smokers and in the...

Full description

Saved in:

Bibliographic Details
Published in:	Respiratory research Vol. 18; no. 1; p. 78
Main Authors:	Aksoy, Mark O, Kim, Victor, Cornwell, William D, Rogers, Thomas J, Kosmider, Beata, Bahmed, Karim, Barrero, Carlos, Merali, Salim, Shetty, Neena, Kelsen, Steven G
Format:	Journal Article
Language:	English
Published:	England BioMed Central 02-05-2017 BMC
Subjects:	Alveoli Biomarker Biomarkers Brefeldin A Bronchus Cell culture Chronic obstructive pulmonary disease Cigarette smoke Cigarettes Conditioning COPD Damage detection Endoplasmic reticulum Epithelial cells Experiments Glucose Golgi apparatus GRP78 Histone deacetylase Intracellular Lungs Lysates Measurement methods Oxidant stress Oxidizing agents Particulates Proteins Respiratory tract Rheumatoid arthritis Secretion Smoke Smoking Western blotting Human Histone deacetylase Biomarker Lung GRP78 Cigarette smoke Oxidant stress COPD
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Identification of biomarkers of cigarette smoke -induced lung damage and early COPD is an area of intense interest. Glucose regulated protein of 78 kD (i.e., GRP78), a multi-functional protein which mediates cell responses to oxidant stress, is increased in the lungs of cigarette smokers and in the serum of subjects with COPD. We have suggested that secretion of GRP78 by lung cells may explain the increase in serum GRP78 in COPD. To assess GRP78 secretion by the lung, we assayed GRP78 in bronchoalveolar lavage fluid (BALF) in chronic smokers and non-smokers. We also directly assessed the acute effect of cigarette smoke material on GRP78 secretion in isolated human airway epithelial cells (HAEC). GRP78 was measured in BALF of smokers (S; n = 13) and non-smokers (NS; n = 11) by Western blotting. GRP78 secretion by HAEC was assessed by comparing its concentration in cell culture medium and cell lysates. Cells were treated for 24 h with either the volatile phase of cigarette smoke (cigarette smoke extract (CSE) or the particulate phase (cigarette smoke condensate (CSC)). GRP78 was present in the BALF of both NS and S but levels were significantly greater in S (p = 0.04). GRP78 was secreted constitutively in HAEC. CSE 15% X 24 h increased GRP78 in cell-conditioned medium without affecting its intracellular concentration. In contrast, CSC X 24 h increased intracellular GRP78 expression but did not affect GRP78 secretion. Brefeldin A, an inhibitor of classical Golgi secretion pathways, did not inhibit GRP78 secretion indicating that non-classical pathways were involved. The present study indicates that GRP78 is increased in BALF in cigarette smokers; that HAEC secrete GRP78; and that GRP78 secretion by HAEC is augmented by cigarette smoke particulates. Enhanced secretion of GRP78 by lung cells makes it a potential biomarker of cigarette smoke-induced lung injury.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1465-993X 1465-9921 1465-993X 1465-9921
DOI:	10.1186/s12931-017-0561-6