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

Abstract

Although alveolar reorganization after acute lung injury depends on regeneration 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 reorganization after injury, we examined expression of C/EBP proteins and mRNAs in lung injuries induced by lipopolysaccharide (LPS) or bleomycin (Bleo) and in cell proliferation by keratinocyte growth factor (KGF). By immunohistochemistry, we demonstrated that C/EBP alpha and C/EBP beta were expressed in alveolar type II cells and alveolar macrophages, but C/EBP delta was expressed restrictedly in some of alveolar type II cells in a spatial pattern in the control lungs. Further, these three C/EBP family members were differentially expressed in alveolar cell proliferation and in acute lung injury, in which, interestingly, C/EBP alpha and C/EBP delta were reciprocally expressed in alveolar type II cell proliferation and in pulmonary fibrosis. However, expressions of their mRNAs by in situ hybridization were dramatically increased in the affected lesions of the lungs by LPS and Bleo, and Northern blot analysis showed an increased abundance of the mRNA for C/EBP beta in LPS-treated lungs and for C/EBP delta in Bleo-treated lungs, compared with those 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.

Keratinocyte growth factor and the transcription factors C/EBPα, C/EBPδ, and SREBP-1c regulate fatty acid synthesis in alveolar type II cells

“…There were smaller increases for C/EBPδ and C/EBPβ in our cultures. C/EBPβ was expressed at high levels in macrophages in vivo, and C/EBPδ showed variable expression in the lung, as described previously (data not shown) (18). SREBP-1 was not detected by in situ in our cultures or in the intact lung, presumably because of the low level of expression.…”

A Novel Pathway for Nickel-induced Interleukin-8 Expression

“…This region of the promoter has not been well studied but does contain putative GATA and C/EBP binding elements. Because both GATA and C/EBP families of binding proteins were implicated in regulating phenotypic change in lung development and injury (31)(32)(33)(34), these sites were the focus of mutational analysis. The data in Fig.…”

JUN-CCAAT/Enhancer-Binding Protein Complexes Inhibit Surfactant-Associated Protein B Promoter Activity

“…In contrast, a deficiency of C/EBP-b and C/ EBP-d did not lead to lung abnormalities (29). However, the expression levels of C/EBP-b, C/EBP-d, and C/EBP-regulated inflammatory mediators are increased in LPS-induced, bleomycininduced, and oxidative stress-induced acute lung injury (26). Here, we investigated the role of C/EBP proteins in the inhibition by JUN of Sftpb promoter activity.…”

“…C/ EBP subfamily members (a, b, and d), in addition to C/EBP-g and C/EBP-z, are expressed and play important roles in lung development, gene regulation, and acute lung injury (22)(23)(24)(25)(26). The…”