Alzheimer's disease is neuropathologically characterized by the accumulation of amyloid-β protein into senile plaques that are sites of chronic inflammation involving reactive microglia, astrocytes, and proinflammatory molecules, such as interleukin-1β and tumor necrosis factor-α. The human CCAAT/enhancer-binding protein (CEBP) delta (CEBPD) is known to be induced in many inflammation-related diseases. In Alzheimer's disease, this protein is responsive to amyloid-β and proinflammatory cytokines in astrocytes. However, the functional role of CEBPD in astrocytes remains largely unclear. In this study, we show that CEBPD is upregulated by interleukin-1β through the mitogen-activated protein kinase p38 (MAPKp38) signaling pathway and phosphorylated by glycogen synthase kinase (GSK)-3β at Ser167 in astrocytes. CEBPD in astrocytes is associated with microglia activation and migration in amyloid precursor protein transgenic mice (AppTg) mice. We further identified that the monocyte chemotactic protein-1, a chemoattractive factor, and migration factors matrix metalloproteinase-1 and -3 are responsive to GSK3β-mediated CEBPD Ser167 phosphorylation. Our results revealed the novel regulation of LiCl on astrocytes and that GSK3β-mediated CEBPD phosphorylation in astrocytes plays an important role in the activation of microglia.

We compared family risk and protective factors among potential high school dropouts with and without suicide-risk behaviors (SRB) and examined the extent to which these factors predict categories of SRB. Subjects were randomly selected from among potential dropouts in 14 high schools. Based upon suicide-risk status, 1,083 potential high school dropouts were defined as belonging to one of four groups; 573 non-suicide risk, 242 low suicide risk, 137 moderate suicide risk and 131 high suicide risk. Results showed significant group differences in all youth self-reported family risk and protective factors. Increased levels of suicide risk were associated with perceived conflict with parents, unmet family goals, and family depression; decreased levels of risk were associated with perceived parental involvement and family support for school. Perceived conflict with parents, family depression, family support satisfaction, and availability of family support for school were the strongest predictors of adolescent SRB. Our findings suggest that suicide vulnerable youth differ from their non-suicidal peers along the dimensions of family risk and protective factors.

CEBPB, one of the CEBP family members, is a crucial regulator of gene expression during innate immunity, inflammatory responses and adipogenesis. In this study, the EGF-induced increase of CEBPB mRNA is shown to be coincident with the decrease of COX-2 mRNA. We identified that all of the individual CEBPB isoforms, LAP1, LAP2 and LIP, attenuate EGF-induced COX-2 promoter activity. Although increased sumoylation of both LAP1 and LAP2 is observed during the lagging stage of EGF treatment, only the sumoylated LAP1, but not the sumoylated LAP2, is responsible for COX-2 gene repression. In addition, EGF treatment can regulate the nucleocytoplasmic redistribution of HDAC4 and SUMO1. We further demonstrated by loss-of- and gain-of-function approaches that HDAC4 can be a negative regulator while inactivating COX-2 transcription. The sumoylation mutant LAP1, LAP1K174A, exhibits an attenuated ability to interact with HDAC4, and increased COX-2 promoter activity. Furthermore, the in vivo DNA binding assay demonstrated that LAP1K174A and CEBPDK120A, sumoylation-defective CEBPD mutants, attenuate the binding of HDAC4 on the COX-2 promoter. In light of the above, our data suggest that the suCEBPD and suLAP1 are involved in the repression of COX-2 transcription through the recruitment of HDAC4.