Inhibitory effect of CXC chemokine receptor 4 antagonist AMD3100 on bleomycin induced murine pulmonary fibrosis

• Published in: Experimental & molecular medicine Vol. 42; no. 6; pp. 465 - 476
• Main Authors: Song, Jeong Sup, Kang, Chun Mi, Kang, Hyeon Hui, Yoon, Hyung Kyu, Kim, Young Kyoon, Kim, Kwan Hyung, Moon, Hwa Sik, Park, Sung Hak
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2010; Springer Nature B.V; Korean Society for Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Bleomycin; Bronchoalveolar Lavage Fluid - chemistry; Cell Movement - drug effects; Cells, Cultured; Chemokine CXCL12 - chemistry; Chemokine CXCL12 - metabolism; Cytoprotection - drug effects; Down-Regulation - drug effects; Drug Evaluation, Preclinical; Female; Heterocyclic Compounds - pharmacology; Heterocyclic Compounds - therapeutic use; Lung - drug effects; Lung - metabolism; Lung - pathology; Medical Biochemistry; Mice; Mice, Inbred C57BL; Molecular Medicine; Original; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - prevention & control; Receptors, CXCR4 - antagonists & inhibitors; Receptors, CXCR4 - metabolism; Stem Cells; 생화학; bleomycin; receptors, CXCR4; chemokine CXCL12; JM 3100; pulmonary fibrosis; chemotaxis
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.3858/emm.2010.42.6.048

CXC chemokine receptor 4 (CXCR4), which binds the stromal cell-derived factor-1 (SDF-1), has been shown to play a critical role in mobilizing the bone marrow (BM)-derived stem cells and inflammatory cells. We studied the effects of AMD3100, CXCR4 antagonist, on a murine bleomycin-induced pulmonary fibrosis model. Treatment of mice with AMD3100 in bleomycin-treated mice resulted in the decrease of SDF-1 in bronchoalveolar lavage (BAL) fluids at an early stage and was followed by the decrease of fibrocytes in the lung. AMD3100 treatment decreased the SDF-1 mRNA expression, fibrocyte numbers in the lung at an early stage (day 3) and CXCR4 expression at the later stage (day 7 and 21) after bleomycin injury. The collagen content and pulmonary fibrosis were significantly attenuated by AMD3100 treatment in later stage of bleomycin injury. AMD3100 treatment also decreased the murine mesenchymal and hematopoietic stem cell chemotaxis when either in the stimulation with bleomycin treated lung lysates or SDF-1 in vitro . In BM stem cell experiments, the phosphorylation of p38 MAPK which was induced by SDF-1 was significantly blocked by addition of AMD3100. Our data suggest that AMD3100 might be effective in preventing the pulmonary fibrosis by inhibiting the fibrocyte mobilization to the injured lung via blocking the SDF-1/CXCR4 axis.