CXCR4 inhibitor attenuates allergen-induced lung inflammation by down-regulating MMP-9 and ERK1/2 |
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| Authors: | Huilong Chen Xiangqin Xu Jieming Teng Sheng Cheng Hansvin Bunjhoo Yong Cao Jin Liu Jungang Xie Congyi Wang Yongjian Xu Weining Xiong |
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| Affiliation: | 1.Department of Respiratory and Critical Care Medicine, Tongji Hospital, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;2.The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China |
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| 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. |
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| Keywords: | Asthma CXCR4 CXCL12 MMP-9 |
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