Disease relevance of Cebpb

• In contrast, transgenic mice bearing a mutationally inactivated NF-IL-6 site showed no increase in transgene expression in hypoxia [1].
• CONCLUSION: Early activation of lung NFkappaB and NF-IL6 and lung cytokine mRNA expression correlated with mortality in polymicrobial sepsis [2].
• These data suggest a potential role for NFkappaB and NF-IL6 activation in the initiation and propagation of acute lung injury [2].
• NF-IL6 (-/-) mice were highly susceptible to infection by Listeria monocytogenes [3].
• Upstream NFIL-6-like site located within a DNase I hypersensitivity region mediates LPS-induced transcription of the murine interleukin-1 beta gene [4].

High impact information on Cebpb

• However, cytokines involved in macrophage activation, such as TNF and IFN gamma, were induced normally in NF-IL6 (-/-) mice [3].
• Furthermore, the tumor cytotoxicity of macrophages from NF-IL6 (-/-) mice was severely impaired [3].
• We also demonstrate that NF-IL6 is essential for the induction of G-CSF in macrophages and fibroblasts [3].
• Electron microscopic observation revealed the escape of a larger number of pathogens from the phagosome to the cytoplasm in activated macrophages from NF-IL6 (-/-) mice [3].
• Nitric oxide (NO) formation was induced to a similar extent in macrophages from both wild-type and NF-IL6 (-/-) mice [3].

Biological context of Cebpb

• Here, we show that Cebpb maps to mouse chromosome 2, Cebpd to chromosome 16, and Cebpe to chromosome 14 [5].
• Furthermore, when the motif of NF-IL6 or NF kappa B or both was subjected to point mutation, the luciferase activity was markedly reduced [6].
• Taken together, these results suggest that regulation of NF-IL6 activity constitutes one of the mechanisms by which PKC-alpha modulates LPS-induced gene expression in the mouse macrophage cell line RAW 264.7 [7].
• Using the electrophoretic mobility shift assay (EMSA) and antibody supershift assay, we were able to qualify the two computationally identified NF-IL6 binding motifs as one high-affinity and one low-affinity binding site [8].
• Chloramphenicol acetyltransferase (CAT) reporter gene assay revealed that NF-IL6 is able to elevate transcription from H2DRE [8].

Anatomical context of Cebpb

• The induction of cyclooxygenase-2 mRNA in macrophages is biphasic and requires both CCAAT enhancer-binding protein beta (C/EBP beta ) and C/EBP delta transcription factors [9].
• PGG-Glucan activates NF-kappaB-like and NF-IL-6-like transcription factor complexes in a murine monocytic cell line [10].
• Finally, LPS-induced expression of two genes regulated by NF-IL6, namely IL-1beta and granulocyte colony-stimulating factor, was impaired in DN PKC-alpha-overexpressing RAW 264.7 cells [7].
• Production of interleukin-6 was markedly increased in B cells of PKC-delta-null mice as a result of an increase in the DNA-binding activity of NF-IL6 [11].
• Granulocyte colony-stimulating factor-induced granulocytic differentiation of multipotential progenitor cells results in activation of C-EBP delta expression and functional recruitment of C-EBP delta and C-EBP beta to the nucleus [12].

Associations of Cebpb with chemical compounds

• Mutations within four regulatory elements, namely, the multiple response element (MRE), AP-1, NF-IL6, and NF-kappa B sites, significantly reduce, but do not completely abrogate, inducibility by cAMP and prostaglandin E1, whereas alterations of four additional sites have no effects [13].
• To explore this issue, we examined nuclear transcriptional regulatory factor (NF-kappaB and NF-IL-6) activation and cytokine expression in the lungs following 12 to 48 h of hyperoxia exposure [14].
• CCAATT/enhancer binding protein (C/EBP)/NFIL-6-driven chloramphenicol acetyltransferase (CAT) reporter activity was sensitive to SB203580, indicating that C/EBP/NFIL-6 transcription factor(s) are also targets of p38 MAPK [15].
• Reporter gene experiments suggested that humulon blocked the cyclooxygenase-2 expression mediated by NFkappaB and NF-IL6, but the intracellular glucocorticoid receptor was not involved [16].
• Nuclear factor-IL6 (NF-IL6) binding was increased at 2 and 8 h with or without LPS in synchronous and delayed synchronous VT-exposure models [17].

Physical interactions of Cebpb

• Region I contains LPS-related responsive elements, including a binding site for nuclear factor interleukin 6 (NF-IL6) and the kappa B binding site for NF-kappa B, suggesting that this region regulates LPS-induced expression of the mac-NOS gene [18].

Regulatory relationships of Cebpb

• Here, we make use of the murine macrophage cells RAW264 as well as of immortalized macrophages derived from mice deficient for the transcription factor CCAAT enhancer-binding protein beta (C/EBP beta) to explore the molecular mechanisms regulating COX-2 induction in activated macrophages [9].
• In contrast, LPS-induced DNA-binding and transcriptional activities of NF-IL6 were inhibited in DN PKC-alpha-overexpressing RAW 264.7 cells and correlated with an impairment of NF-IL6 nuclear translocation [7].
• Base substitutions within this NFIL-6 site resulted in virtual elimination of LPS-induced IL-1 beta gene transcription [4].
• Correlation between lentinan-specific IL-6 mRNA expression (the late expression) controlled recessively and DT-APR induction suggests that the ltn1 loci control some process(es) of IL-6 expression in the regulation step before NF-IL6 [19].
• Inhibition of xanthine oxidase by prior feeding of a tungsten-enriched diet prevented hemorrhage-induced activation in lung cells of NF-kappa B. Incubating splenocytes in vitro with xanthine oxidase activated NF-kappa B but not NF-IL6 [20].

Other interactions of Cebpb

• In the present study, we have investigated the impact of PKC-alpha on the activation of AP-1 and NF-IL6 in LPS-treated RAW 264.7 macrophages [7].
• We conclude that the H2-K(b) gene belongs to target genes of the NF-IL6 (C/EBPbeta) in the course of the cellular response to TNF-alpha, and we discuss some consequences of this conclusion in a general framework of inducible expression of the H2-K(b) gene [8].
• A DNA probe including the NF-IL6 and AP2 sites gave positive bands upon electrophoretic mobility shift assay using the nuclear extracts of MC3T3-E1 cells [6].
• Similarly, TNF-induced activation of activator protein 1 or NF-IL-6 was not impaired in FAK-/- cells [21].
• Although IL-6 mRNA levels correlated with NFkappaB and NF-IL6 activation, tumor necrosis factor-alpha mRNA levels did not, in that they preceded transcription factor activation [2].

Analytical, diagnostic and therapeutic context of Cebpb

• This study investigated the activation of lung nuclear factor kappaB (NFkappaB) and nuclear factor interleukin-6 (NF-IL6) and how they correlate to proinflammatory cytokine expression and mortality in a murine model of cecal ligation and puncture (CLP) [2].
• To investigate the role of NF-IL6 in vivo, we have generated NF-IL6 (-/-) mice by gene targeting [3].
• Western blotting revealed that bFGF increased NFIL-6 protein at 2 h [22].
• Immunofluorescence analysis of MC3T3-E1 cells showed primarily cytoplasmic and perinuclear NFIL-6 staining in control cultures while bFGF-treated cells showed increased NFIL-6 staining at 2 and 4 h [22].
• Sequence analysis of the proximal promoter region revealed the presence of a TATA box and putative transcription factor-binding sites, such as those for NF-kappaB and NF-IL6 [23].

References