| HIF-1α inhibition ameliorates an allergic airway disease via VEGF suppression in bronchial epithelium. | |
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MedLine Citation:
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PMID:Â 20827786 Â Â Â Owner:Â NLM Â Â Â Status:Â MEDLINE Â Â Â |
Abstract/OtherAbstract:
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Hypoxia-inducible factor-1α (HIF-1α) plays a critical role in immune and inflammatory responses. One of the HIF-1α target genes is vascular endothelial growth factor (VEGF), which is a potent stimulator of inflammation, airway remodeling, and physiologic dysregulation in allergic airway diseases. Using OVA-treated mice and murine tracheal epithelial cells, the signaling networks involved in HIF-1α activation and the role of HIF-1α in the pathogenesis of allergic airway disease were investigated. Transfection of airway epithelial cells with HIF-1α siRNA suppressed VEGF expression. In addition, the increased levels of HIF-1α and VEGF in lung tissues after OVA inhalation were substantially decreased by an HIF-1α inhibitor, 2-methoxyestradiol. Our data also show that the increased numbers of inflammatory cells, increased airway hyperresponsiveness, levels of IL-4, IL-5, IL-13, and vascular permeability in the lungs after OVA inhalation were significantly reduced by 2-methoxyestradiol or a VEGF inhibitor, CBO-P11. Moreover, we found that inhibition of the PI3K p110δ isoform (PI3K-δ) or HIF-1α reduced OVA-induced HIF-1α activation in airway epithelial cells. These findings indicate that HIF-1α inhibition may attenuate antigen-induced airway inflammation and hyperresponsiveness through the modulation of vascular leakage mediated by VEGF, and that PI3K-δ signaling may be involved in the allergen-induced HIF-1α activation. |
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Authors:
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So Ri Kim; Kyung Sun Lee; Hee Sun Park; Seoung Ju Park; Kyung Hoon Min; Hee Moon; Kamal D Puri; Yong Chul Lee |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't    |
Journal Detail:
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Title: European journal of immunology    Volume: 40    ISSN: 1521-4141    ISO Abbreviation: Eur. J. Immunol.    Publication Date: 2010 Oct |
Date Detail:
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Created Date:Â 2010-11-01 Â Â Â Completed Date:Â 2010-12-16 Â Â Â Revised Date:Â - Â Â Â |
Medline Journal Info:
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Nlm Unique ID: 1273201    Medline TA: Eur J Immunol    Country: Germany    |
Other Details:
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Languages: eng    Pagination: 2858-69    Citation Subset: IM    |
Affiliation:
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Department of Internal Medicine and Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenine
/
analogs & derivatives,Â
pharmacology Airway Remodeling / immunology* Animals Asthma / immunology* Bronchoalveolar Lavage Fluid / chemistry, cytology Endothelial Growth Factors / pharmacology Epithelial Cells Estradiol / analogs & derivatives, pharmacology Female Histocytochemistry Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*, genetics, immunology* Mice Mice, Inbred C57BL Ovalbumin / immunology Peptides, Cyclic / pharmacology Phosphatidylinositol 3-Kinases / antagonists & inhibitors, immunology Quinazolines / pharmacology RNA / chemistry, genetics RNA, Small Interfering / pharmacology Respiratory Function Tests Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / immunology Specific Pathogen-Free Organisms Vascular Endothelial Growth Factor A / antagonists & inhibitors*, genetics, immunology* |
| Chemical | |
Reg. No./Substance:
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0/Endothelial Growth Factors; 0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/IC 87114; 0/Peptides, Cyclic; 0/Quinazolines; 0/RNA, Small Interfering; 0/Vascular Endothelial Growth Factor A; 0/cyclo-VEGI; 362-07-2/2-methoxyestradiol; 50-28-2/Estradiol; 63231-63-0/RNA; 73-24-5/Adenine; 9006-59-1/Ovalbumin; EC 2.7.1.-/Phosphatidylinositol 3-Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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