| First Author | Xu J | Year | 2006 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 291 |
| Issue | 4 | Pages | L658-67 |
| PubMed ID | 16648243 | Mgi Jnum | J:144409 |
| Mgi Id | MGI:3830901 | Doi | 10.1152/ajplung.00006.2006 |
| Citation | Xu J, et al. (2006) Increased bleomycin-induced lung injury in mice deficient in the transcription factor T-bet. Am J Physiol Lung Cell Mol Physiol 291(4):L658-67 |
| abstractText | The reasons for variable sensitivity among and within species to lung injury and fibrosis caused by bleomycin (BLM) are unknown. Because T helper (Th) 1 and 2 (Th1 and Th2) polarization of CD4+ T lymphocytes is one of the factors that affects the BLM response, we hypothesized that preventing expression of the Th1 transcription factor T-bet would render BLM-resistant BALB/c mice sensitive to BLM. Wild-type and T-bet-deficient (T-bet-/-) BALB/c mice were treated with BLM or saline solution intratracheally. After BLM treatment, collagen content in the lung increased twofold by day 14 in lungs from T-bet-/- mice but was unaffected in lungs from wild-type BALB/c mice. These findings were confirmed by collagen staining of histopathological sections. BLM treatment significantly increased respiratory frequency and decreased tidal volume by day 14 in T-bet-/- mice but had no effect in wild-type mice. Lung fibrosis in BLM-treated T-bet-/- mice was associated with increased circulating levels of Th2 cytokines and increased expression of the profibrotic factor transforming growth factor-beta1. Depletion of CD4+, but not CD8+, T cells in T-bet-/- mice diminished BLM-induced lung fibrosis and the expression of transforming growth factor-beta1. These data suggest that the T-bet pathway in CD4+ T lymphocytes can confer resistance to BLM-induced lung fibrosis in BALB/c mice. |
