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Azithromycin Attenuates Fibroblast Growth Factors Induced Vascular Endothelial Growth Factor Via p38(MAPK) Signaling in Human Airway Smooth Muscle Cells.
MedLine Citation:
PMID:  22205500     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The airways in asthma and COPD are characterized by an increase in airway smooth muscle (ASM) mass and bronchial vascular changes associated with increased expression of pro-angiogenic growth factors, such as fibroblast growth factors (FGF-1 and FGF-2) and vascular endothelial growth factor (VEGF). We investigated the contribution of FGF-1/-2 in VEGF production in ASM cells and assessed the influence of azithromycin and dexamethasone and their underlying signaling mechanisms. Growth-synchronized human ASM cells were pre-treated with MAPK inhibitors, U0126 for ERK1/2(MAPK) and SB239063 for p38(MAPK) as well as with dexamethasone or azithromycin, 30 min before incubation with FGF-1 or FGF-2. Expression of VEGF (VEGF-A, VEGF(121), and VEGF(165)) was assessed by quantitative PCR, VEGF release by ELISA and MAPK phosphorylation by Western blotting. Both FGF-1 and FGF-2 significantly induced mRNA levels of VEGF-A, VEGF(121), and VEGF(165). The VEGF protein release was increased 1.8-fold (FGF-1) and 5.5-fold (FGF-2) as compared to controls. Rapid transient increase in ERK1/2(MAPK) and p38(MAPK) phosphorylation and subsequent release of VEGF from FGF-1 or FGF-2-treated ASM cells were inhibited by respective blockers. Furthermore, azithromycin and dexamethasone significantly reduced both the VEGF release and the activation of p38(MAPK) pathway in response to FGF-1 or FGF-2 treatment. Our Results demonstrate that FGF-1 and FGF-2 up-regulate VEGF production via ERK1/2(MAPK) and p38(MAPK) pathways. Both azithromycin and dexamethasone elicited their anti-angiogenic effects via p38(MAPK) pathway in vitro, thereby suggesting a possible therapeutic approach to tackle VEGF-mediated vascular remodeling.
Authors:
Anna Willems-Widyastuti; Bart M Vanaudenaerde; Robin Vos; Ellen Dilisen; Stijn E Verleden; Stéphanie I De Vleeschauwer; Annemie Vaneylen; Wolter J Mooi; Willem I de Boer; Hari S Sharma; Geert M Verleden
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-29
Journal Detail:
Title:  Cell biochemistry and biophysics     Volume:  -     ISSN:  1559-0283     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9701934     Medline TA:  Cell Biochem Biophys     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium.
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