Increased bleomycin-induced lung injury in mice deficient of the transcription factor T-bet

and Mauricio Rojas. Increased bleomycin-induced lung injury in mice deficient in the transcription factor T-bet. Am J Physiol Lung Cell Mol Physiol 291: L658–L667, 2006. First published April 28, 2006; doi:10.1152/ajplung.00006.2006.—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 prevent-ing 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