Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP

H. Y. Oh, S. Namkoong, S. J. Lee, E. Por, C. K. Kim, T. R. Billiar, J. A. Han, K. S. Ha, H. T. Chung, Y. G. Kwon, H. Lee, Y. M. Kim

Research output: Contribution to journalArticle

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Abstract

Dexamethasone (DEX) pretreatment protected hepatocytes from TNF-α plus actinomycin D (ActD)-induced apoptosis by suppressing caspase-8 activation and the mitochondria-dependent apoptosis pathway. DEX treatment upregulated cellular FLICE inhibitory protein (cFLIP) expression, but did not alter the protein levels of Bcl-2, Bcl-xL, Mcl-1, and cIAP as well as Akt activation. The increased cFLIP mRNA level by DEX was inhibited by ActD, indicating that DEX upregulates cFLIP expression at the transcriptional step. DEX also inhibited Jo2-mediated hepatocyte apoptosis by blocking the formation of the death-inducing signaling complex and caspase-8 activation. Specific downregulation of cFLIP expression using siRNA reversed the antiapoptotic effect of DEX by increasing caspase-8 activation. Moreover, DEX administration into mice increased cFLIP expression in the liver and prevented Jo2-induced hepatic injury by inhibiting caspase-8 and -3 activities. Our results indicate that DEX exerts a protective role in death receptor-induced in vitro and in vivo hepatocyte apoptosis by upregulating cFLIP expression.

Original languageEnglish
Pages (from-to)512-523
Number of pages12
JournalCell Death and Differentiation
Volume13
Issue number3
DOIs
Publication statusPublished - 2006 Mar 1

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CASP8 and FADD-Like Apoptosis Regulating Protein
Death Domain Receptors
Dexamethasone
Hepatocytes
Up-Regulation
Apoptosis
Caspase 8
Dactinomycin
Death Domain Receptor Signaling Adaptor Proteins
Liver
Caspase 3
Small Interfering RNA
Mitochondria
Down-Regulation
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Oh, H. Y. ; Namkoong, S. ; Lee, S. J. ; Por, E. ; Kim, C. K. ; Billiar, T. R. ; Han, J. A. ; Ha, K. S. ; Chung, H. T. ; Kwon, Y. G. ; Lee, H. ; Kim, Y. M. / Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP. In: Cell Death and Differentiation. 2006 ; Vol. 13, No. 3. pp. 512-523.
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Oh, HY, Namkoong, S, Lee, SJ, Por, E, Kim, CK, Billiar, TR, Han, JA, Ha, KS, Chung, HT, Kwon, YG, Lee, H & Kim, YM 2006, 'Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP', Cell Death and Differentiation, vol. 13, no. 3, pp. 512-523. https://doi.org/10.1038/sj.cdd.4401771

Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP. / Oh, H. Y.; Namkoong, S.; Lee, S. J.; Por, E.; Kim, C. K.; Billiar, T. R.; Han, J. A.; Ha, K. S.; Chung, H. T.; Kwon, Y. G.; Lee, H.; Kim, Y. M.

In: Cell Death and Differentiation, Vol. 13, No. 3, 01.03.2006, p. 512-523.

Research output: Contribution to journalArticle

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AU - Kim, C. K.

AU - Billiar, T. R.

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AU - Ha, K. S.

AU - Chung, H. T.

AU - Kwon, Y. G.

AU - Lee, H.

AU - Kim, Y. M.

PY - 2006/3/1

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N2 - Dexamethasone (DEX) pretreatment protected hepatocytes from TNF-α plus actinomycin D (ActD)-induced apoptosis by suppressing caspase-8 activation and the mitochondria-dependent apoptosis pathway. DEX treatment upregulated cellular FLICE inhibitory protein (cFLIP) expression, but did not alter the protein levels of Bcl-2, Bcl-xL, Mcl-1, and cIAP as well as Akt activation. The increased cFLIP mRNA level by DEX was inhibited by ActD, indicating that DEX upregulates cFLIP expression at the transcriptional step. DEX also inhibited Jo2-mediated hepatocyte apoptosis by blocking the formation of the death-inducing signaling complex and caspase-8 activation. Specific downregulation of cFLIP expression using siRNA reversed the antiapoptotic effect of DEX by increasing caspase-8 activation. Moreover, DEX administration into mice increased cFLIP expression in the liver and prevented Jo2-induced hepatic injury by inhibiting caspase-8 and -3 activities. Our results indicate that DEX exerts a protective role in death receptor-induced in vitro and in vivo hepatocyte apoptosis by upregulating cFLIP expression.

AB - Dexamethasone (DEX) pretreatment protected hepatocytes from TNF-α plus actinomycin D (ActD)-induced apoptosis by suppressing caspase-8 activation and the mitochondria-dependent apoptosis pathway. DEX treatment upregulated cellular FLICE inhibitory protein (cFLIP) expression, but did not alter the protein levels of Bcl-2, Bcl-xL, Mcl-1, and cIAP as well as Akt activation. The increased cFLIP mRNA level by DEX was inhibited by ActD, indicating that DEX upregulates cFLIP expression at the transcriptional step. DEX also inhibited Jo2-mediated hepatocyte apoptosis by blocking the formation of the death-inducing signaling complex and caspase-8 activation. Specific downregulation of cFLIP expression using siRNA reversed the antiapoptotic effect of DEX by increasing caspase-8 activation. Moreover, DEX administration into mice increased cFLIP expression in the liver and prevented Jo2-induced hepatic injury by inhibiting caspase-8 and -3 activities. Our results indicate that DEX exerts a protective role in death receptor-induced in vitro and in vivo hepatocyte apoptosis by upregulating cFLIP expression.

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