Influenza A infection results in lung cell apoptosis, injury, and remodeling

f C/EBPb in LY3039478 web IL-1b-induced IL6 production, we transfected MLE12 cells with control siRNA or siRNA specific for C/EBPb. As shown in Fig. 6A, C/EBPb siRNA almost completely abrogated C/EBPb expression compared with control siRNA in MLE12 cells. Furthermore, knockdown of C/ EBPb expression significantly decreased IL-1b-induced IL-6 expression at both mRNA and protein levels. We further examined the role of C/EBb in IL-1b-induced IL-6 expression in transfection study using IL-6 promoter-luciferase assay. Consistent with the results from RT-PCR and ELISAs, IL-1b stimulation alone induced a 2.5-fold increase of C/EBPc Suppresses IL-6 Production 4 C/EBPc Suppresses IL-6 Production luciferase activity compared with control group. Moreover, IL-1b treatment of C/EBPb transfectants led to a 25% increase of luciferase activity than the IL-1b stimulation alone. C/EBPc suppresses IL-1b-induced IL-6 expression by inhibiting C/EBPb activity but not NF-kB activity We reason that C/EBPc suppresses the IL-6 expression through inhibiting stimulatory C/EBP acitivity. MLE 12 cells were transfected with 26C/EBP-Luc, a C/EBP-dependent promoterreporter containing two copies of a C/EBP binding site, together with C/EBPc expressing plasmid or control plasmid. As shown in Fig. 7A, IL-1b stimulation led to a significant increase of 26C/ EBP-Luc expression, and over-expression of C/EBPc resulted in a reduction of luciferase activity to the basal level. In sharp contrast, although there is a more than 2-fold IL-1b induction of kBLuciferase expression, this activity was not affected by C/EBPc expression. We further show that C/EBPc overexpression caused a significant decrease of the “6145492 26C/EBP-Luc expression induced by C/EBPb over-expression. To determine if decreased C/EBPb binding by C/EBPc could lead to the reduced IL-6 expression, MLE 12 cells were transfected with C/EBPb plasmid in the presence or absence of C/EBPc plasmid. As shown in Fig. 7D, C/EBPb itself caused a 1.7-fold increase of IL-6-Luc expression, while over-expression of C/EBPc led to a significant decrease of the luciferase expression. Together, these data suggest that C/EBPc inhibits 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 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 expr