Differential expression of CCAAT enhancer binding protein family in rat alveolar epithelial cell proliferation and in acute lung injury

Although alveolar reorganization after acute lung injury depends on regener ation of alveolar epithelial cells, there is little knowledge of regulation of pulmonary healing process. Transcription factors may play key roles in this regulation. To investigate whether the CCAAT enhancer binding protein (C/EBP) family, alpha, beta, and delta, were involved in alveolar reorganiz ation after injury, we examined expression of C/EBP proteins and mRNAs in l ung injuries induced by lipopolysaccharide (LPS) or bleomycin (Bleo) and in cell proliferation by keratinocyte growth factor (KGF). By immunohistochem istry, we demonstrated that C/EBP alpha and C/EBP beta were expressed in al veolar type II cells and alveolar macrophages, but C/EBP delta was expresse d restrictedly in some of alveolar type II cells in a spatial pattern in th e control lungs. Further, these three C/EBP family members were differentia lly expressed in alveolar cell proliferation and in acute lung injury, in w hich, interestingly, C/EBP alpha and C/EBP delta were reciprocally expresse d in alveolar type II cell proliferation and in pulmonary fibrosis. However , expressions of their mRNAs by in situ hybridization were dramatically inc reased in the affected lesions of the lungs by LPS and Bleo, and Northern b lot analysis showed an increased abundance of the mRNA for C/EBP beta in LP S-treated lungs and for C/EBP delta in Bleo-treated lungs, compared with th ose in the control lungs. Thus, differential expression of the C/EBP family may be required to maintain and reorganize the basic integrity of alveolar structure during pathological states, which suggests an important role for the C/EBP family in maintaining normal alveolar architecture and function and in repairing the damaged epithelium after injury.