NFκB Mediates Apoptosis through Transcriptional Activation of Fas (CD95) in Adenoviral Hepatitis

Kühnel, Florian; Zender, Lars; Paul, Yasmin; Tietze, Maja Katrin; Trautwein, Christian; Manns, Michael P.; Kubicka, Stefan

doi:10.1074/jbc.275.9.6421

Cited by 164 publications

(113 citation statements)

References 70 publications

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“…nF-κB regulates expression of many genes (for example, IκB-α, bcl-2, Il-6 and cyclin D1). suppression of nF-κB activation is known as a key to induction of apoptosis in many cell lines (3,12,17,27,28). In our experiments Scutellaria baicalensis slightly inhibited expression of nF-κB p65 in B-1F cells in the presence of e2.…”

Section: Discussionsupporting

confidence: 54%

Possible mechanism of growth inhibition by Scutellaria baicalensis in an estrogen-responsive mouse tumor cell line

Murashima

Katayama²,

Shojiro³

et al. 2011

Oncol Rep

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Abstract.We have studied the effects of saiboku-to, a traditional chinese medicine having suppressive activities for leukotriene production and release, on the proliferation of the estrogen-responsive mouse leydig tumor cell line B-1F. In our previous reports, it is shown that saiboku-to promotes, but Scutellaria baicalensis, one of the components (herbs) of Saiboku-to, significantly inhibits the proliferation of B-1F cells in vitro and in vivo, and induces DnA fragmentation and morphological changes such as nuclear aggregation and fragmentation. In this study, we examined telomerase activity, cell cycle, polyunsaturated fatty acid metabolism and expression of nuclear factor κB (nF-κB) in order to determine the mechanism of growth inhibition in B-1F cells treated with Scutellaria baicalensis. telomerase activity was decreased in a dose-dependent manner in treated B-1F cells. cellular populations in the sub-g0/g1 and g2/M phases were increased, but those in M phase had no change. Although cyclin D1 mrnA was highly expressed in the presence of estradiol (e2), cyclin A and E mRNA levels did not significantly change. When B-1F cells were treated with Scutellaria baicalensis, expression of cyclin D1 was suppressed and that of p21 was inversely increased. Moreover, Scutellaria baicalensis influenced arachidonic and linoleic acid metabolism, and increased production of 13(s)-HoDe. In the presence of e2 Scutellaria baicalensis decreased expression of nF-κB p65 to 0.71-fold in B-1F cells. these results show that Scutellaria baicalensis might induce cell cycle arrest at g1 phase and apoptosis via inhibition of telomerase activity, changes of enzymatic activities in polyunsaturated fatty acid metabolism and suppression of nF-κB.

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Section: Discussionsupporting

confidence: 54%

Possible mechanism of growth inhibition by Scutellaria baicalensis in an estrogen-responsive mouse tumor cell line

Murashima

Katayama²,

Shojiro³

et al. 2011

Oncol Rep

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“…We observed a transient up-regulation of NF-B in hepatocytes after CD40 ligation, which peaked at 2 h and was back at baseline by 4 h. Many proapoptotic genes also have NF-B binding sites on their promoters, for example, FasL (Kasibhatla et al, 1999), Fas receptor (Gil et al, 1999;Kuhnel et al, 2000), and p53 (Wu and Lozano, 1994), and it is possible that the transient induction of NF-B may be critical in up-regulating FasL expression (Holtz-Heppelmann et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Differential Induction of Nuclear Factor-κB and Activator Protein-1 Activity after CD40 Ligation Is Associated with Primary Human Hepatocyte Apoptosis or Intrahepatic Endothelial Cell Proliferation

Choudhury

Russell

Randhawa

et al. 2003

MBoC

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CD40, a tumor necrosis factor receptor superfamily member, is up-regulated on intraheptatic endothelial cells (IHEC) and epithelial cells during inflammatory liver disease, and there is evidence that the functional outcome of CD40 ligation differs between cell types. Ligation of CD40 on cholangiocytes or hepatocytes results in induction of Fas-mediated apoptosis, whereas ligation of IHEC CD40 leads to enhanced chemokine secretion and adhesion molecule expression. We now report that differential activation of two transcription factors, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), in primary human hepatocytes or IHEC, is associated with and may explain, in part, the different responses of these cell types to CD40 ligation. CD40 ligation induced a rise in NF-κB activity in hepatocytes ,which peaked at 2 h and returned to baseline by 24 h; however, IHEC CD40 ligation resulted in a sustained up-regulation of NF-κB (>24 h). In hepatocytes, CD40 ligation led to sustained up-regulation of AP-1 activity >24 h associated with increased protein levels of RelA (p65), c-Jun, and c-Fos, whereas no induction of AP-1 activity was observed in IHECs. Analysis of mitogen-activated protein kinase phosphorylation (phospho-extracellular signal-regulated kinase 1/2 and phospho-c-Jun NH2-terminal kinase 1/2) and expression of inhibitor κBα were entirely consistent, and thus confirmed the profiles of NF-κB and AP-1 signaling and the effects of the selective inhibitors assessed using electrophoretic mobility shift assay or Western immunoblotting. CD40 ligation resulted in induction of apoptosis in hepatocytes after 24 h, but on IHECs, CD40 ligation resulted in proliferation. Inhibition of (CD40-mediated) NF-κB activation prevented IHEC proliferation and led to induction of apoptosis. Selective extracellular signal-regulated kinase and c-Jun NH2-terminal kinase inhibitors reduced levels of apoptosis in (CD40-stimulated) hepatocytes by ∼50%. We conclude that differential activation of these two transcription factors in response to CD40 ligation is associated with differences in cell fate. Transient activation of NF-κB and sustained AP-1 activation is associated with apoptosis in hepatocytes, whereas prolonged NF-κB activation and a lack of AP-1 activation in IHECs result in proliferation.

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“…In addition, a crucial role for NF-kB in induction of Fas expression has been demonstrated (Ouaaz et al, 1999;Ku¨hnel et al, 2000). To identify which components of secretory phenotype are modulated by NF-kB in premature senescent tumor cells, we knocked-down expression of RelA, the main member of the NF-kB family, in MCF-7 and A549 cells by using lentiviruses encoding small hairpin RNA.…”

Section: Nf-kb Modulates Sasp and Fas Expressionmentioning

confidence: 99%

NF-κB-dependent cytokine secretion controls Fas expression on chemotherapy-induced premature senescent tumor cells

et al. 2011

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Induction of a senescent phenotype in tumor cells has been linked to anticancer immune response, however, the molecular mechanisms mediating these phenomenon have not yet been determined. In this study, we present evidence that induction of premature senescence in human cancer cell lines induces Fas expression, and loss of resistance to Fas-induced apoptosis. Triggering of Fas by using the agonistic antibody CH11 or the recombinant ligand APO010, activates an apoptotic pathway responsible for cell death. Secretion of pro-inflammatory cytokines by the senescent cells, particularly TNF-a and IFN-c, mediates Fas upregulation. Indeed, treatment of proliferating cancer cell lines with TNF-a and IFN-c, upregulates Fas expression, while blocking TNF-a and IFN-c by using neutralizing antibodies, decreases Fas expression in senescent cells. We also demonstrate that NF-jB has a central role in controlling the senescence-associated secretory phenotype (SASP) by the premature senescent cells, and that TNF-a and IFN-c, transcriptionally controlled by NF-jB, are the main mediators of Fas upregulation. Our data suggest the existence of an NF-jB-dependent autocrine loop, mediated by TNF-a and IFN-c, responsible for expression of Fas on the surface of senescent cells, and for their killing.

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NFκB Mediates Apoptosis through Transcriptional Activation of Fas (CD95) in Adenoviral Hepatitis

Cited by 164 publications

References 70 publications

Possible mechanism of growth inhibition by Scutellaria baicalensis in an estrogen-responsive mouse tumor cell line

Possible mechanism of growth inhibition by Scutellaria baicalensis in an estrogen-responsive mouse tumor cell line

Differential Induction of Nuclear Factor-κB and Activator Protein-1 Activity after CD40 Ligation Is Associated with Primary Human Hepatocyte Apoptosis or Intrahepatic Endothelial Cell Proliferation

NF-κB-dependent cytokine secretion controls Fas expression on chemotherapy-induced premature senescent tumor cells

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