ne and inflammatory responses by mediating activation of alveolar type II epithelial cells, leading to pro-inflammatory cytokine production such as IL-6. IL-6, which is a pleiotropic cytokine produced by a variety of cell populations such as alveolar macrophages and alveolar type II cells, plays an important role in both acute and chronic lung injury. IL-6 expression is mainly regulated at transcriptional 6 C/EBPc Suppresses IL-6 Production level, which is controlled by a variety of transcription factors binding to the cis-acting elements of the IL-6 promoter region, such as NF-kB and C/EBPb/d. For example, C/EBPb and -d have both been shown to activate a reporter gene controlled by the IL-6 promoter in transient expression assays. Furthermore, the stable expression of C/EBPb in a murine B lymphoblast cell line is sufficient to confer LPS inducibility of IL-6 expression. Importantly, NF-kB and C/EBPb synergistically activate the IL-6 promoter, and consistent with this, direct interaction between the C/EBPb bZIP and the NF-kB Rel homology domain has been observed, as well as cooperative binding of the two factors. In addition, the NF-kB site of the IL-6 promoter is required for the activity of the C/EBPb bZIP in the absence of aminoterminal G5555 motifs. All of these studies suggested a mechanism for IL-6 activation whose essential feature is the requirement for the bZIP region of C/EPBb to synergize with NF-kB, although this remains to be further investigated. In addition, it has been recently shown that IL-1b-induced IL-6 production in alveolar type II cells is associated with the activation of both IL-1 receptorassociated kinase-4 and phosphatidylinositol 3-kinase. However, in alveolar type II cells, molecular mechanisms involved in IL-1b-induced IL-6 production remains largely unknown. In the current study, we find that the binding activity of both NF-kB and C/EBPb to 
their regulatory elements in the IL-6 promoter is significantly elevated 23416332” by IL-1b stimulation in alveolar epithelial cells. Our data further indicate that both C/EBPb and p65 are indispensable for IL-1b-induced IL-6 expression, which 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 10460232” 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-