Dual effect of AMD3100, a CXCR4 antagonist, on bleomycin-induced lung inflammation
| Autor: | Masaki Watanabe, Hideo Mitsuyama, Mitsuhiro Osame, Satoshi Noma, Yuko Shirahama, Ikkou Higashimoto, Kimiyoshi Arimura, Ken-ichi Oonakahara, Wataru Matsuyama |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Chemokine
Benzylamines Receptors CXCR4 Anti-HIV Agents Neutrophils Pulmonary Fibrosis Immunology Inflammation Pharmacology Bleomycin Cyclams CXCR4 Chemokine receptor chemistry.chemical_compound Mice Heterocyclic Compounds Pulmonary fibrosis Nitriles Butadienes Immunology and Allergy Medicine Animals Mitogen-Activated Protein Kinase 1 Lung CXCR4 antagonist Mitogen-Activated Protein Kinase 3 biology business.industry Pneumonia respiratory system medicine.disease respiratory tract diseases Mice Inbred C57BL medicine.anatomical_structure chemistry biology.protein Cytokines Female medicine.symptom business Bronchoalveolar Lavage Fluid |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 178(9) |
| ISSN: | 0022-1767 |
| Popis: | The chemokine receptor CXCR4, which binds the chemokine stromal cell-derived factor 1, has been reported to be involved in the chemotaxis of inflammatory cells. In addition, AMD3100, an antagonist of CXCR4, has been reported to be an attractive drug candidate for therapeutic intervention in several disorders in which CXCR4 is critically involved. However, little is known about the therapeutic value of AMD3100 in the treatment of pulmonary fibrosis. In this study, we examined the effects of AMD3100 on a murine bleomycin-induced pulmonary fibrosis model. Concurrent administration of AMD3100 and bleomycin apparently attenuated bleomycin-induced pulmonary inflammation. In this process, an inhibition of neutrophil recruitment at early stage followed by the decrease of other inflammatory cell recruitment in the lung were observed. In addition, it also inhibited the expression of cytokines, including MCP-1, MIP-2, MIP-1α, and TGF-β. In contrast, when AMD3100 was administered following bleomycin treatment, the bleomycin-induced lung inflammation progressed and resulted in severe pulmonary fibrosis. In this process, an increase of inflammatory cell recruitment, an up-regulation of lung MCP-1 and TGF-β, and a remarkable activation of p44/42 MAPK in neutrophils were observed. U0126, an inhibitor of p44/42 MAPK, significantly abolished these effects. Thus, AMD3100 has dual effect on bleomycin-induced pulmonary fibrosis. Difference of inflammatory cell recruitment and activation might be associated with the dual effect of AMD3100 on bleomycin-induced pulmonary fibrosis. |
| Databáze: | OpenAIRE |
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