Different Activity of the Biological Axis VEGF-Flt-1 (fms-Like Tyrosine Kinase 1) and CXC Chemokines between Pulmonary Sarcoidosis and Idiopathic Pulmonary Fibrosis: A Bronchoalveolar Lavage Study

Background. We have previously shown a different local and systemic angiogenic profile of CXC chemokines in Idiopathic Pulmonary Fibrosis (IPF) patients compared to sarcoidosis. In particular, sarcoidosis showed an angiostatic microenvironment, as compared with the angiogenic cytokine milieu seen in...

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Main Authors: Katerina M. Antoniou, Giannoula Soufla, Athanasia Proklou, George Margaritopoulos, Christiana Choulaki, Rena Lymbouridou, Katerina D. Samara, Demetrios A. Spandidos, Nikolaos M. Siafakas
Format: Article
Language:English
Published: Wiley 2009-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2009/537929
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author Katerina M. Antoniou
Giannoula Soufla
Athanasia Proklou
George Margaritopoulos
Christiana Choulaki
Rena Lymbouridou
Katerina D. Samara
Demetrios A. Spandidos
Nikolaos M. Siafakas
author_facet Katerina M. Antoniou
Giannoula Soufla
Athanasia Proklou
George Margaritopoulos
Christiana Choulaki
Rena Lymbouridou
Katerina D. Samara
Demetrios A. Spandidos
Nikolaos M. Siafakas
author_sort Katerina M. Antoniou
collection DOAJ
description Background. We have previously shown a different local and systemic angiogenic profile of CXC chemokines in Idiopathic Pulmonary Fibrosis (IPF) patients compared to sarcoidosis. In particular, sarcoidosis showed an angiostatic microenvironment, as compared with the angiogenic cytokine milieu seen in IPF. Purpose of the Study. Our aim was to further investigate the aforementioned finding by measuring the expression of different chemokines in granulomatous and fibrotic diseases. We estimated the levels of vascular endothelial growth factor (VEGF) and its high-affinity receptor, Flt-1 (fms-like tyrosine kinase 1), in bronchoalveolar lavage fluid (BALF) of patients with IPF and pulmonary sarcoidosis. We have also investigated the mRNA expression of angiogenetic chemokines' receptors such as CXCR2 and CXCR3 and the biological axis of stromal derived factor-1𝛼 (SDF-1𝛼 or CXCL12𝛼/CXCL12𝛽) and receptor, CXCR4. Methods. We studied prospectively three groups of patients: (i) one group of 18 patients with IPF, (ii) one group of 16 patients with sarcoidosis, and (iii) 10 normal subjects. Results. A statistically significant increase has been detected in VEGF mRNA expression in IPF in comparison with pulmonary sarcoidosis (𝑃=.03). In addition, a significant increase has been measured in CXCL12𝛼 in sarcoidosis in comparison to IPF (𝑃=.02). Moreover, a statistically significant decrease has been found in Flt-1 protein levels in pulmonary sarcoidosis in comparison with IPF (𝑃=.03). A significant increase in VEGF (𝑃=.03) and CXCR4 (𝑃=.03) mRNA levels has been also detected in sarcoidosis' patients when compared with healthy controls. Conclusions. Our data suggest that increased expression of Flt-1 and downregulation of CXCL12𝛼 in IPF may further support the hypothesis of a different angiogenetic profile between fibrotic and granulomatous diseases. However, further studies are needed in order to better investigate these enigmatic diseases.
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spelling doaj-art-e77567e47dfd4b2297f025a503396a692025-02-03T07:24:30ZengWileyClinical and Developmental Immunology1740-25221740-25302009-01-01200910.1155/2009/537929537929Different Activity of the Biological Axis VEGF-Flt-1 (fms-Like Tyrosine Kinase 1) and CXC Chemokines between Pulmonary Sarcoidosis and Idiopathic Pulmonary Fibrosis: A Bronchoalveolar Lavage StudyKaterina M. Antoniou0Giannoula Soufla1Athanasia Proklou2George Margaritopoulos3Christiana Choulaki4Rena Lymbouridou5Katerina D. Samara6Demetrios A. Spandidos7Nikolaos M. Siafakas8Department of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion, 71110 Crete, GreeceLaboratory of Virology, Medical School, University of Crete, Heraklion, GreeceDepartment of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion, 71110 Crete, GreeceDepartment of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion, 71110 Crete, GreeceDepartment of Rheumatology, Clinical Immunology and Allergy, University Hospital, University of Crete, Heraklion, GreeceLaboratory of Virology, Medical School, University of Crete, Heraklion, GreeceDepartment of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion, 71110 Crete, GreeceLaboratory of Virology, Medical School, University of Crete, Heraklion, GreeceDepartment of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion, 71110 Crete, GreeceBackground. We have previously shown a different local and systemic angiogenic profile of CXC chemokines in Idiopathic Pulmonary Fibrosis (IPF) patients compared to sarcoidosis. In particular, sarcoidosis showed an angiostatic microenvironment, as compared with the angiogenic cytokine milieu seen in IPF. Purpose of the Study. Our aim was to further investigate the aforementioned finding by measuring the expression of different chemokines in granulomatous and fibrotic diseases. We estimated the levels of vascular endothelial growth factor (VEGF) and its high-affinity receptor, Flt-1 (fms-like tyrosine kinase 1), in bronchoalveolar lavage fluid (BALF) of patients with IPF and pulmonary sarcoidosis. We have also investigated the mRNA expression of angiogenetic chemokines' receptors such as CXCR2 and CXCR3 and the biological axis of stromal derived factor-1𝛼 (SDF-1𝛼 or CXCL12𝛼/CXCL12𝛽) and receptor, CXCR4. Methods. We studied prospectively three groups of patients: (i) one group of 18 patients with IPF, (ii) one group of 16 patients with sarcoidosis, and (iii) 10 normal subjects. Results. A statistically significant increase has been detected in VEGF mRNA expression in IPF in comparison with pulmonary sarcoidosis (𝑃=.03). In addition, a significant increase has been measured in CXCL12𝛼 in sarcoidosis in comparison to IPF (𝑃=.02). Moreover, a statistically significant decrease has been found in Flt-1 protein levels in pulmonary sarcoidosis in comparison with IPF (𝑃=.03). A significant increase in VEGF (𝑃=.03) and CXCR4 (𝑃=.03) mRNA levels has been also detected in sarcoidosis' patients when compared with healthy controls. Conclusions. Our data suggest that increased expression of Flt-1 and downregulation of CXCL12𝛼 in IPF may further support the hypothesis of a different angiogenetic profile between fibrotic and granulomatous diseases. However, further studies are needed in order to better investigate these enigmatic diseases.http://dx.doi.org/10.1155/2009/537929
spellingShingle Katerina M. Antoniou
Giannoula Soufla
Athanasia Proklou
George Margaritopoulos
Christiana Choulaki
Rena Lymbouridou
Katerina D. Samara
Demetrios A. Spandidos
Nikolaos M. Siafakas
Different Activity of the Biological Axis VEGF-Flt-1 (fms-Like Tyrosine Kinase 1) and CXC Chemokines between Pulmonary Sarcoidosis and Idiopathic Pulmonary Fibrosis: A Bronchoalveolar Lavage Study
Clinical and Developmental Immunology
title Different Activity of the Biological Axis VEGF-Flt-1 (fms-Like Tyrosine Kinase 1) and CXC Chemokines between Pulmonary Sarcoidosis and Idiopathic Pulmonary Fibrosis: A Bronchoalveolar Lavage Study
title_full Different Activity of the Biological Axis VEGF-Flt-1 (fms-Like Tyrosine Kinase 1) and CXC Chemokines between Pulmonary Sarcoidosis and Idiopathic Pulmonary Fibrosis: A Bronchoalveolar Lavage Study
title_fullStr Different Activity of the Biological Axis VEGF-Flt-1 (fms-Like Tyrosine Kinase 1) and CXC Chemokines between Pulmonary Sarcoidosis and Idiopathic Pulmonary Fibrosis: A Bronchoalveolar Lavage Study
title_full_unstemmed Different Activity of the Biological Axis VEGF-Flt-1 (fms-Like Tyrosine Kinase 1) and CXC Chemokines between Pulmonary Sarcoidosis and Idiopathic Pulmonary Fibrosis: A Bronchoalveolar Lavage Study
title_short Different Activity of the Biological Axis VEGF-Flt-1 (fms-Like Tyrosine Kinase 1) and CXC Chemokines between Pulmonary Sarcoidosis and Idiopathic Pulmonary Fibrosis: A Bronchoalveolar Lavage Study
title_sort different activity of the biological axis vegf flt 1 fms like tyrosine kinase 1 and cxc chemokines between pulmonary sarcoidosis and idiopathic pulmonary fibrosis a bronchoalveolar lavage study
url http://dx.doi.org/10.1155/2009/537929
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