An essential role for CCAAT/enhancer binding protein ?? in bleomycin-induced pulmonary fibrosis No conflicts of interest were declared.

Pulmonary fibrosis is characterized by inflammation, genesis of myofibroblasts, and abnormal tissue repair. Despite extensive research, its pathogenesis remains incompletely understood. Previously, the transcription factor CCAAT/enhancer binding protein ?? (C/EBP??) was found to be a key regulator of myofibroblast differentiation in vitro , and to be involved in the acute phase and inflammatory responses. In an attempt to test the role of C/EBP?? in the development of pulmonary fibrosis, experiments using C/EBP ?? null mice and their wild-type littermates were conducted. Our findings indicated that, compared to wild-type mice, animals deficient in C/EBP?? showed significantly reduced fibrotic lesions and collagen deposition in the lung upon endotracheal injection of bleomycin. Further studies on the mechanisms by which C/EBP?? regulates fibrosis indicated that knockout of C/EBP ?? attenuates inflammatory cytokine expression in bleomycin-treated mice. The reduced ??-smooth muscle actin gene expression in either isolated lung fibroblasts or lung tissue from bleomycin or saline-treated C/EBP?? deficient mice suggests that C/EBP?? regulates myofibroblast differentiation during fibrosis. Consistent with this finding, cells from C/EBP?? deficient mice exhibited higher proliferative rates than those from wild-type mice. These data suggest that C/EBP?? plays an essential role in pulmonary fibrosis and that this role appears to be multifactorial with respect to cytokine expression, cell differentiation, and proliferation. Copyright ?? 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.