| First Author | He C | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 28 | Pages | 20745-57 |
| PubMed ID | 23720777 | Mgi Jnum | J:201791 |
| Mgi Id | MGI:5515703 | Doi | 10.1074/jbc.M112.410720 |
| Citation | He C, et al. (2013) Accelerated development of pulmonary fibrosis via Cu,Zn-superoxide dismutase-induced alternative activation of macrophages. J Biol Chem 288(28):20745-57 |
| abstractText | Macrophages not only initiate and accentuate inflammation after tissue injury, but they are also involved in resolution and repair. This difference in macrophage activity is the result of a differentiation process to either M1 or M2 phenotypes. M1 macrophages are pro-inflammatory and have microbicidal and tumoricidal activity, whereas the M2 macrophages are involved in tumor progression and tissue remodeling and can be profibrotic in certain conditions. Because mitochondrial Cu,Zn-superoxide dismutase (Cu,Zn-SOD)-mediated H2O2 is crucial for development of pulmonary fibrosis, we hypothesized that Cu,Zn-SOD modulated the macrophage phenotype. In this study, we demonstrate that Cu,Zn-SOD polarized macrophages to an M2 phenotype, and Cu,Zn-SOD-mediated H2O2 levels modulated M2 gene expression at the transcriptional level by redox regulation of a critical cysteine in STAT6. Furthermore, overexpression of Cu,Zn-SOD in mice resulted in a profibrotic environment and accelerated the development of pulmonary fibrosis, whereas polarization of macrophages to the M1 phenotype attenuated pulmonary fibrosis. Taken together, these observations provide a novel mechanism of Cu,Zn-SOD-mediated and Th2-independent M2 polarization and provide a potential therapeutic target for attenuating the accelerated development of pulmonary fibrosis. |
