c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis.

Xuehua Piao; Sachiko Komazawa-Sakon; Takashi Nishina; Masato Koike; Jiang-Hu Piao; Hanno Ehlken; Hidetake Kurihara; Mutsuko Hara; Van Rooijen Nico; Günther Schütz; Masaki Ohmuraya; Yasuo Uchiyama; Hideo Yagita; Ko Okumura; You-Wen He; Hiroyasu Nakano

c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis.

Standard

c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis. / Piao, Xuehua; Komazawa-Sakon, Sachiko; Nishina, Takashi; Koike, Masato; Piao, Jiang-Hu; Ehlken, Hanno; Kurihara, Hidetake; Hara, Mutsuko; Nico, Van Rooijen; Schütz, Günther; Ohmuraya, Masaki; Uchiyama, Yasuo; Yagita, Hideo; Okumura, Ko; He, You-Wen; Nakano, Hiroyasu.

In: SCI SIGNAL, Vol. 5, No. 255, 255, 2012, p. 93.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Piao, X, Komazawa-Sakon, S, Nishina, T, Koike, M, Piao, J-H, Ehlken, H, Kurihara, H, Hara, M, Nico, VR, Schütz, G, Ohmuraya, M, Uchiyama, Y, Yagita, H, Okumura, K, He, Y-W & Nakano, H 2012, 'c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis.', SCI SIGNAL, vol. 5, no. 255, 255, pp. 93. <http://www.ncbi.nlm.nih.gov/pubmed/23250397?dopt=Citation>

APA

Piao, X., Komazawa-Sakon, S., Nishina, T., Koike, M., Piao, J-H., Ehlken, H., Kurihara, H., Hara, M., Nico, V. R., Schütz, G., Ohmuraya, M., Uchiyama, Y., Yagita, H., Okumura, K., He, Y-W., & Nakano, H. (2012). c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis. SCI SIGNAL, 5(255), 93. [255]. http://www.ncbi.nlm.nih.gov/pubmed/23250397?dopt=Citation

Vancouver

Piao X, Komazawa-Sakon S, Nishina T, Koike M, Piao J-H, Ehlken H et al. c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis. SCI SIGNAL. 2012;5(255):93. 255.

Bibtex

@article{d589151007304a129f5fc610538f8a96,

title = "c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis.",

abstract = "As a catalytically inactive homolog of caspase-8, a proapoptotic initiator caspase, c-FLIP blocks apoptosis by binding to and inhibiting caspase-8. The transcription factor nuclear factor ?B (NF-?B) plays a pivotal role in maintaining the homeostasis of the intestine and the liver by preventing death receptor-induced apoptosis, and c-FLIP plays a role in the NF-?B-dependent protection of cells from death receptor signaling. Because c-Flip-deficient mice die in utero, we generated conditional c-Flip-deficient mice to investigate the contribution of c-FLIP to homeostasis of the intestine and the liver at developmental and postnatal stages. Intestinal epithelial cell (IEC)- or hepatocyte-specific deletion of c-Flip resulted in perinatal lethality as a result of the enhanced apoptosis and programmed necrosis of the IECs and the hepatocytes. Deficiency in the gene encoding tumor necrosis factor-? (TNF-?) receptor 1 (Tnfr1) partially rescued perinatal lethality and the development of colitis in IEC-specific c-Flip-deficient mice but did not rescue perinatal lethality in hepatocyte-specific c-Flip-deficient mice. Moreover, adult mice with interferon (IFN)-inducible deficiency in c-Flip died from hepatitis soon after depletion of c-FLIP. Pretreatment of IFN-inducible c-Flip-deficient mice with a mixture of neutralizing antibodies against TNF-?, Fas ligand (FasL), and TNF-related apoptosis-inducing ligand (TRAIL) prevented hepatitis. Together, these results suggest that c-FLIP controls the homeostasis of IECs and hepatocytes by preventing cell death induced by TNF-?, FasL, and TRAIL.",

keywords = "Animals, Mice, Mice, Mutant Strains, *Apoptosis, Caspase 8, NF-kappa B/genetics/metabolism, *Homeostasis, Antibodies, Neutralizing/pharmacology, CASP8 and FADD-Like Apoptosis Regulating Protein/genetics/*metabolism, Colitis/genetics/metabolism/pathology, Fas Ligand Protein/antagonists & inhibitors/genetics/metabolism, Hepatitis/genetics/metabolism/pathology, Hepatocytes/*metabolism/pathology, Intestines/*metabolism/pathology, Liver/*metabolism/pathology, Necrosis/genetics/metabolism/pathology, Organ Specificity/drug effects/genetics, Protein Binding/drug effects/genetics, Receptors, Tumor Necrosis Factor, Type I/genetics/metabolism, TNF-Related Apoptosis-Inducing Ligand/genetics/metabolism, Tumor Necrosis Factor-alpha/antagonists & inhibitors/genetics/metabolism, Animals, Mice, Mice, Mutant Strains, *Apoptosis, Caspase 8, NF-kappa B/genetics/metabolism, *Homeostasis, Antibodies, Neutralizing/pharmacology, CASP8 and FADD-Like Apoptosis Regulating Protein/genetics/*metabolism, Colitis/genetics/metabolism/pathology, Fas Ligand Protein/antagonists & inhibitors/genetics/metabolism, Hepatitis/genetics/metabolism/pathology, Hepatocytes/*metabolism/pathology, Intestines/*metabolism/pathology, Liver/*metabolism/pathology, Necrosis/genetics/metabolism/pathology, Organ Specificity/drug effects/genetics, Protein Binding/drug effects/genetics, Receptors, Tumor Necrosis Factor, Type I/genetics/metabolism, TNF-Related Apoptosis-Inducing Ligand/genetics/metabolism, Tumor Necrosis Factor-alpha/antagonists & inhibitors/genetics/metabolism",

author = "Xuehua Piao and Sachiko Komazawa-Sakon and Takashi Nishina and Masato Koike and Jiang-Hu Piao and Hanno Ehlken and Hidetake Kurihara and Mutsuko Hara and Nico, {Van Rooijen} and G{\"u}nther Sch{\"u}tz and Masaki Ohmuraya and Yasuo Uchiyama and Hideo Yagita and Ko Okumura and You-Wen He and Hiroyasu Nakano",

year = "2012",

language = "English",

volume = "5",

pages = "93",

journal = "SCI SIGNAL",

issn = "1945-0877",

publisher = "American Association for the Advancement of Science",

number = "255",

}

RIS

TY - JOUR

T1 - c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis.

AU - Piao, Xuehua

AU - Komazawa-Sakon, Sachiko

AU - Nishina, Takashi

AU - Koike, Masato

AU - Piao, Jiang-Hu

AU - Ehlken, Hanno

AU - Kurihara, Hidetake

AU - Hara, Mutsuko

AU - Nico, Van Rooijen

AU - Schütz, Günther

AU - Ohmuraya, Masaki

AU - Uchiyama, Yasuo

AU - Yagita, Hideo

AU - Okumura, Ko

AU - He, You-Wen

AU - Nakano, Hiroyasu

PY - 2012

Y1 - 2012

N2 - As a catalytically inactive homolog of caspase-8, a proapoptotic initiator caspase, c-FLIP blocks apoptosis by binding to and inhibiting caspase-8. The transcription factor nuclear factor ?B (NF-?B) plays a pivotal role in maintaining the homeostasis of the intestine and the liver by preventing death receptor-induced apoptosis, and c-FLIP plays a role in the NF-?B-dependent protection of cells from death receptor signaling. Because c-Flip-deficient mice die in utero, we generated conditional c-Flip-deficient mice to investigate the contribution of c-FLIP to homeostasis of the intestine and the liver at developmental and postnatal stages. Intestinal epithelial cell (IEC)- or hepatocyte-specific deletion of c-Flip resulted in perinatal lethality as a result of the enhanced apoptosis and programmed necrosis of the IECs and the hepatocytes. Deficiency in the gene encoding tumor necrosis factor-? (TNF-?) receptor 1 (Tnfr1) partially rescued perinatal lethality and the development of colitis in IEC-specific c-Flip-deficient mice but did not rescue perinatal lethality in hepatocyte-specific c-Flip-deficient mice. Moreover, adult mice with interferon (IFN)-inducible deficiency in c-Flip died from hepatitis soon after depletion of c-FLIP. Pretreatment of IFN-inducible c-Flip-deficient mice with a mixture of neutralizing antibodies against TNF-?, Fas ligand (FasL), and TNF-related apoptosis-inducing ligand (TRAIL) prevented hepatitis. Together, these results suggest that c-FLIP controls the homeostasis of IECs and hepatocytes by preventing cell death induced by TNF-?, FasL, and TRAIL.

AB - As a catalytically inactive homolog of caspase-8, a proapoptotic initiator caspase, c-FLIP blocks apoptosis by binding to and inhibiting caspase-8. The transcription factor nuclear factor ?B (NF-?B) plays a pivotal role in maintaining the homeostasis of the intestine and the liver by preventing death receptor-induced apoptosis, and c-FLIP plays a role in the NF-?B-dependent protection of cells from death receptor signaling. Because c-Flip-deficient mice die in utero, we generated conditional c-Flip-deficient mice to investigate the contribution of c-FLIP to homeostasis of the intestine and the liver at developmental and postnatal stages. Intestinal epithelial cell (IEC)- or hepatocyte-specific deletion of c-Flip resulted in perinatal lethality as a result of the enhanced apoptosis and programmed necrosis of the IECs and the hepatocytes. Deficiency in the gene encoding tumor necrosis factor-? (TNF-?) receptor 1 (Tnfr1) partially rescued perinatal lethality and the development of colitis in IEC-specific c-Flip-deficient mice but did not rescue perinatal lethality in hepatocyte-specific c-Flip-deficient mice. Moreover, adult mice with interferon (IFN)-inducible deficiency in c-Flip died from hepatitis soon after depletion of c-FLIP. Pretreatment of IFN-inducible c-Flip-deficient mice with a mixture of neutralizing antibodies against TNF-?, Fas ligand (FasL), and TNF-related apoptosis-inducing ligand (TRAIL) prevented hepatitis. Together, these results suggest that c-FLIP controls the homeostasis of IECs and hepatocytes by preventing cell death induced by TNF-?, FasL, and TRAIL.

KW - Animals

KW - Mice

KW - Mice, Mutant Strains

KW - Apoptosis

KW - Caspase 8

KW - NF-kappa B/genetics/metabolism

KW - Homeostasis

KW - Antibodies, Neutralizing/pharmacology

KW - CASP8 and FADD-Like Apoptosis Regulating Protein/genetics/metabolism

KW - Colitis/genetics/metabolism/pathology

KW - Fas Ligand Protein/antagonists & inhibitors/genetics/metabolism

KW - Hepatitis/genetics/metabolism/pathology

KW - Hepatocytes/metabolism/pathology

KW - Intestines/metabolism/pathology

KW - Liver/metabolism/pathology

KW - Necrosis/genetics/metabolism/pathology

KW - Organ Specificity/drug effects/genetics

KW - Protein Binding/drug effects/genetics

KW - Receptors, Tumor Necrosis Factor, Type I/genetics/metabolism

KW - TNF-Related Apoptosis-Inducing Ligand/genetics/metabolism

KW - Tumor Necrosis Factor-alpha/antagonists & inhibitors/genetics/metabolism