ibits Crenolanib web IL-1b-induced IL-6 expression by suppressing C/EBPb activity. Discussion Previous study shows that C/EBPc dramatically augments the activity of C/EBPb in “7901789 LPS induction of the IL-6 and IL-8 promoters in a B lymphoblast cell line. In another study, Kaisho et al show that the ability of C/EBPc chimera splenocytes to produce interferon c in response to IL-12 and/or IL-18 was markedly impaired. To our knowledge, these are the only two reports indicating a possible role of C/EBPc in C/EBPc Suppresses IL-6 Production regulating the expression of inflammatory mediators. In this study, we show that C/EBPc expression is induced by IL-1b in alveolar type II epithelial cells. We further show that C/EBPc is a critical regulator of IL-1b-mediated IL-6 production. Although alveolar type II epithelial cells only cover about 5% of the alveolar surface area, there is increasing evidence that they play a significant role in lung inflammatory diseases. IL-1b is a critical inducer of immune 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 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 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