ch is consistent with the observation in other cell types. Our finding that C/EBPc can regulate IL-1b-induced IL-6 production in alveolar type II epithelial cells is interesting. C/ EBPc has been considered as an inhibitor of other C/EBP family members. For example, C/EBPc inhibits C/EBPb-mediated HIV-1 long terminal repeat-driven transcription in human brain cells. In addition, C/EBPc represses C/EBPb-mediated induction of alcohol dehydrogenase expression in the rat livers. These results are consistent with the fact that C/EBPc lacks known activation domains and is essentially a C/EBP bZIP domain. In contrast, C/EBPc can also act as a transcription activator. For example, C/EBPc has been shown to be a positive regulator of IFN-c expression in splenocytes and NK cells, and gamma-globin expression in fetal liver. Furthermore, previous studies demonstrated 
that augmentation of C/EBPb activity on the IL-6 and IL-8 promoters by C/EBPc required formation of a heterodimeric leucine zipper and co-expression of NF-kB. Interestingly, C/EBPc inhibits C/EBPb- and C/ EBPd-mediated transactivation of a reporter gene in fibroblasts in a leucine zipper-dependent manner, but it has no suppressive function in HepG2 hepatoma cells. These findings together indicate that C/EBPc has complex effects on gene transcription. Our current finding that C/EBPc suppresses IL-1b-induced IL-6 production in alveolar type II epithelial cells further suggests that its function may be cell specific. The exact molecular mechanism whereby C/EBPc regulates gene expression is not clear. In IL-1b-stimulated alveolar epithelial cells, C/EBPc exists as both homodimers and heterodimers . It is possible that the lack of one transactivation domain in C/EBPc:b heterodimers may contribute to the inhibitory effect of C/EBPc. On the other hand, in C/EBPc-overexpressed cells, the major C/EBPc binding species is C/EBPc:c homodimers, suggesting that C/ EBPc:c homodimers may compete with the stimulatory C/EBP b:b to bind to IL-6 promoter region. In addition, we observed an increased C/EBPc:b heterodimers binding to IL-6 promoter in C/EBPc-overexpressed cells C/EBPc Suppresses IL-6 Production 8 C/EBPc Suppresses IL-6 Production . This suggests that there is a free C/ EBPb pool in the nucleus. However, whether C/EBPc is a preferential dimerization partner for C/EBPb or C/EBPc:b heterodimers have a higher affinity than C/EBPb:b in lung epithelial cells remains an open question. Interestingly, C/EBPc does not seem to affect NF-kB DNA binding, suggesting that C/EBPc has no effect on the get Selumetinib synergistic activity between NF-kB and C/EBPb in IL-6 promoter in alveolar epithelial cells. Taken together, we identified a previously unrecognized role for C/EBPc in inflammation in alveolar epithelial cells. Not surprisingly, many transcription factors such as NF-kB and C/ EBPb are activated in the acute lung inflammatory reaction. However, our current study suggests that the acute inflammatory response in the lung can also be counter-regulated by other transcription factors such as C/EBPc. Understanding the underlying roles and mechanisms whereby C/EBPc regulates the network of inflammatory system in the lung may be a crucial step for the development of new therapeutic targets for treatment of lung inflammatory diseases. Materials and Methods Cells and Reagents Murine lung epithelial cells and HEK293 cells were obtained from American Type Culture Collection, and cultured in DMEM/F-12 supplemented with 5% fet
