Abstract
Chemokine (C-X-C motif) ligand 12 (CXCL12) and its receptor chemokine receptor 4 (CXCR4) have been recognized to play a crucial role in the pathogenesis of bronchial asthma, but the underlying molecular mechanisms are yet to be fully addressed. In the present report we demonstrated that CXCL12/CXCR4 signaling mediates allergic airway inflammation through induction of matrix metalloproteinase 9 (MMP-9) in a murine asthmatic model. We noted that administration of AMD3100, a specific CXCR4 antagonist, significantly attenuated OVA-induced asthmatic responses along with reduced epithelial MMP-9 expression. Our studies in a bronchial epithelial cell line, 16HBE cells, further revealed that CXCL12/CXCR4 signaling synergizes with IL-13 to enhance epithelial MMP-9 expression. Our mechanistic studies demonstrated that CXCL12/CXCR4 enhances epithelial MMP-9 expression by inducing ERK1/2 expression and activation. Together, these studies would bring novel insight into the understanding for the role of CXCL12/CXCR4 signaling in asthmatic responses during the course of bronchial asthma development.
Keywords:
Asthma; CXCL12; CXCR4; MMP-9.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allergens
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Animals
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Anti-Asthmatic Agents / pharmacology*
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Anti-Inflammatory Agents / pharmacology*
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Asthma / drug therapy*
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Asthma / enzymology
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Asthma / immunology
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Benzylamines
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Bronchi / drug effects*
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Bronchi / enzymology
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Bronchi / immunology
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Cell Line
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Chemokine CXCL12 / metabolism
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Cyclams
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Disease Models, Animal
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Down-Regulation
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Enzyme Activation
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Epithelial Cells / drug effects*
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Epithelial Cells / enzymology
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Epithelial Cells / immunology
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Female
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Heterocyclic Compounds / pharmacology*
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Humans
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Interleukin-13 / metabolism
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Matrix Metalloproteinase 9 / metabolism*
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase 1 / metabolism*
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Mitogen-Activated Protein Kinase 3 / metabolism*
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Ovalbumin
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Pneumonia / drug therapy*
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Pneumonia / enzymology
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Pneumonia / immunology
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Receptors, CXCR4 / antagonists & inhibitors*
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Receptors, CXCR4 / immunology
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Receptors, CXCR4 / metabolism
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Signal Transduction / drug effects
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Time Factors
Substances
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Allergens
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Anti-Asthmatic Agents
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Anti-Inflammatory Agents
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Benzylamines
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CXCL12 protein, human
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CXCR4 protein, human
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CXCR4 protein, mouse
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Chemokine CXCL12
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Cxcl12 protein, mouse
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Cyclams
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Heterocyclic Compounds
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Interleukin-13
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Receptors, CXCR4
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Ovalbumin
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MAPK1 protein, human
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Mapk1 protein, mouse
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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MMP9 protein, human
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Matrix Metalloproteinase 9
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Mmp9 protein, mouse
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