Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers
Abstract Background 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...
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12931-017-0561-6 |
| _version_ | 1811226617315328000 |
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| author | Mark O. Aksoy Victor Kim William D. Cornwell Thomas J. Rogers Beata Kosmider Karim Bahmed Carlos Barrero Salim Merali Neena Shetty Steven G. Kelsen |
| author_facet | Mark O. Aksoy Victor Kim William D. Cornwell Thomas J. Rogers Beata Kosmider Karim Bahmed Carlos Barrero Salim Merali Neena Shetty Steven G. Kelsen |
| author_sort | Mark O. Aksoy |
| collection | DOAJ |
| description | Abstract Background 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). Methods 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)). Results 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. Conclusion 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. |
| first_indexed | 2024-04-12T09:28:08Z |
| format | Article |
| id | doaj.art-9661c7fac6544bb69122ed0b711aaa9a |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-12T09:28:08Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-9661c7fac6544bb69122ed0b711aaa9a2022-12-22T03:38:26ZengBMCRespiratory Research1465-993X2017-05-011811810.1186/s12931-017-0561-6Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokersMark O. Aksoy0Victor Kim1William D. Cornwell2Thomas J. Rogers3Beata Kosmider4Karim Bahmed5Carlos Barrero6Salim Merali7Neena Shetty8Steven G. Kelsen9Department of Thoracic Medicine and Surgery, Temple University School of MedicineDepartment of Thoracic Medicine and Surgery, Temple University School of MedicineDepartment of Thoracic Medicine and Surgery, Temple University School of MedicineDepartment of Thoracic Medicine and Surgery, Temple University School of MedicineDepartment of Thoracic Medicine and Surgery, Temple University School of MedicineDepartment of Thoracic Medicine and Surgery, Temple University School of MedicineTemple University School of PharmacyTemple University School of PharmacyDepartment of Thoracic Medicine and Surgery, Temple University School of MedicineDepartment of Thoracic Medicine and Surgery, Temple University School of MedicineAbstract Background 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). Methods 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)). Results 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. Conclusion 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.http://link.springer.com/article/10.1186/s12931-017-0561-6Oxidant stressGRP78Cigarette smokeCOPDHistone deacetylaseBiomarker |
| spellingShingle | Mark O. Aksoy Victor Kim William D. Cornwell Thomas J. Rogers Beata Kosmider Karim Bahmed Carlos Barrero Salim Merali Neena Shetty Steven G. Kelsen Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers Respiratory Research Oxidant stress GRP78 Cigarette smoke COPD Histone deacetylase Biomarker |
| title | Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers |
| title_full | Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers |
| title_fullStr | Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers |
| title_full_unstemmed | Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers |
| title_short | Secretion of the endoplasmic reticulum stress protein, GRP78, into the BALF is increased in cigarette smokers |
| title_sort | secretion of the endoplasmic reticulum stress protein grp78 into the balf is increased in cigarette smokers |
| topic | Oxidant stress GRP78 Cigarette smoke COPD Histone deacetylase Biomarker |
| url | http://link.springer.com/article/10.1186/s12931-017-0561-6 |
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