1-Methyl-L-Tryptophan promotes the apoptosis of hepatic stellate cells arrested by interferon-γ by increasing the expression of IFN-γRβ, IRF-1 and FAS

Ji Eun Oh, Kwang Yong Shim, Jong In Lee, Soo In Choi, Soon Koo Baik, Young Woo Eom

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4 Citations (Scopus)

Abstract

Liver fibrosis, a precursor to cirrhosis, is the result of the deposition of extracellular matrix (ECM) proteins and is mediated primarily by activated hepatic stellate cells (HSCs). In this study, we investigated the anti-fibrotic effects of interferon (IFN)γ in activated HSCs in vitro and whether cell viability would be decreased by the inhibition of indoleamine 2,3-dioxygemase (IDO), which is responsible for cell cycle arrest. Following treatment with IFN-γ, cell signaling pathways and DNA content were analyzed to assess the inactivation of HSCs or the decrease in HSC proliferation. The IDO inhibitor, 1-methyl-L-Tryptophan (1-MT), was used to determine whether IDO plays a key role in the regulation of activated HSCs, as IFNγ increases the expression of IDO. IFN-γ significantly inhibited the growth of HSCs and downregulated the expression of α-smooth muscle actin (α-SMA) in the HSCs. IDO expression was markedly increased by IFN-γ through signal transducer and activator of transcription 1 (STAT1) activation and resulted in the depletion of tryptophan. This depletion induced G1 cell cycle arrest. When the cells were released from IFN-γ-mediated G1 cell cycle arrest by treatment with 1-MT, the apoptosis of the HSCs was markedly increased through the induction of IFN-γRβ, interferon regulatory factor (IRF-1) and FAS. Our results thus suggest that the inhibition of IDO enhances the suppression of activated HSCs, and therefore co-Treatment with IFN-γ and 1-MT may be applied to ameliorate liver fibrosis.

Original languageEnglish
Pages (from-to)576-582
Number of pages7
JournalInternational journal of molecular medicine
Volume40
Issue number2
DOIs
Publication statusPublished - 2017 Aug

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Hepatic Stellate Cells
Tryptophan
Interferons
Apoptosis
G1 Phase Cell Cycle Checkpoints
Liver Cirrhosis
Interferon Regulatory Factor-1
STAT1 Transcription Factor
tryptophan methyl ester
Extracellular Matrix Proteins
Cell Cycle Checkpoints
Transcriptional Activation
Smooth Muscle
Actins
Cell Survival
Fibrosis
Down-Regulation
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

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title = "1-Methyl-L-Tryptophan promotes the apoptosis of hepatic stellate cells arrested by interferon-γ by increasing the expression of IFN-γRβ, IRF-1 and FAS",
abstract = "Liver fibrosis, a precursor to cirrhosis, is the result of the deposition of extracellular matrix (ECM) proteins and is mediated primarily by activated hepatic stellate cells (HSCs). In this study, we investigated the anti-fibrotic effects of interferon (IFN)γ in activated HSCs in vitro and whether cell viability would be decreased by the inhibition of indoleamine 2,3-dioxygemase (IDO), which is responsible for cell cycle arrest. Following treatment with IFN-γ, cell signaling pathways and DNA content were analyzed to assess the inactivation of HSCs or the decrease in HSC proliferation. The IDO inhibitor, 1-methyl-L-Tryptophan (1-MT), was used to determine whether IDO plays a key role in the regulation of activated HSCs, as IFNγ increases the expression of IDO. IFN-γ significantly inhibited the growth of HSCs and downregulated the expression of α-smooth muscle actin (α-SMA) in the HSCs. IDO expression was markedly increased by IFN-γ through signal transducer and activator of transcription 1 (STAT1) activation and resulted in the depletion of tryptophan. This depletion induced G1 cell cycle arrest. When the cells were released from IFN-γ-mediated G1 cell cycle arrest by treatment with 1-MT, the apoptosis of the HSCs was markedly increased through the induction of IFN-γRβ, interferon regulatory factor (IRF-1) and FAS. Our results thus suggest that the inhibition of IDO enhances the suppression of activated HSCs, and therefore co-Treatment with IFN-γ and 1-MT may be applied to ameliorate liver fibrosis.",
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1-Methyl-L-Tryptophan promotes the apoptosis of hepatic stellate cells arrested by interferon-γ by increasing the expression of IFN-γRβ, IRF-1 and FAS. / Oh, Ji Eun; Shim, Kwang Yong; Lee, Jong In; Choi, Soo In; Baik, Soon Koo; Eom, Young Woo.

In: International journal of molecular medicine, Vol. 40, No. 2, 08.2017, p. 576-582.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 1-Methyl-L-Tryptophan promotes the apoptosis of hepatic stellate cells arrested by interferon-γ by increasing the expression of IFN-γRβ, IRF-1 and FAS

AU - Oh, Ji Eun

AU - Shim, Kwang Yong

AU - Lee, Jong In

AU - Choi, Soo In

AU - Baik, Soon Koo

AU - Eom, Young Woo

PY - 2017/8

Y1 - 2017/8

N2 - Liver fibrosis, a precursor to cirrhosis, is the result of the deposition of extracellular matrix (ECM) proteins and is mediated primarily by activated hepatic stellate cells (HSCs). In this study, we investigated the anti-fibrotic effects of interferon (IFN)γ in activated HSCs in vitro and whether cell viability would be decreased by the inhibition of indoleamine 2,3-dioxygemase (IDO), which is responsible for cell cycle arrest. Following treatment with IFN-γ, cell signaling pathways and DNA content were analyzed to assess the inactivation of HSCs or the decrease in HSC proliferation. The IDO inhibitor, 1-methyl-L-Tryptophan (1-MT), was used to determine whether IDO plays a key role in the regulation of activated HSCs, as IFNγ increases the expression of IDO. IFN-γ significantly inhibited the growth of HSCs and downregulated the expression of α-smooth muscle actin (α-SMA) in the HSCs. IDO expression was markedly increased by IFN-γ through signal transducer and activator of transcription 1 (STAT1) activation and resulted in the depletion of tryptophan. This depletion induced G1 cell cycle arrest. When the cells were released from IFN-γ-mediated G1 cell cycle arrest by treatment with 1-MT, the apoptosis of the HSCs was markedly increased through the induction of IFN-γRβ, interferon regulatory factor (IRF-1) and FAS. Our results thus suggest that the inhibition of IDO enhances the suppression of activated HSCs, and therefore co-Treatment with IFN-γ and 1-MT may be applied to ameliorate liver fibrosis.

AB - Liver fibrosis, a precursor to cirrhosis, is the result of the deposition of extracellular matrix (ECM) proteins and is mediated primarily by activated hepatic stellate cells (HSCs). In this study, we investigated the anti-fibrotic effects of interferon (IFN)γ in activated HSCs in vitro and whether cell viability would be decreased by the inhibition of indoleamine 2,3-dioxygemase (IDO), which is responsible for cell cycle arrest. Following treatment with IFN-γ, cell signaling pathways and DNA content were analyzed to assess the inactivation of HSCs or the decrease in HSC proliferation. The IDO inhibitor, 1-methyl-L-Tryptophan (1-MT), was used to determine whether IDO plays a key role in the regulation of activated HSCs, as IFNγ increases the expression of IDO. IFN-γ significantly inhibited the growth of HSCs and downregulated the expression of α-smooth muscle actin (α-SMA) in the HSCs. IDO expression was markedly increased by IFN-γ through signal transducer and activator of transcription 1 (STAT1) activation and resulted in the depletion of tryptophan. This depletion induced G1 cell cycle arrest. When the cells were released from IFN-γ-mediated G1 cell cycle arrest by treatment with 1-MT, the apoptosis of the HSCs was markedly increased through the induction of IFN-γRβ, interferon regulatory factor (IRF-1) and FAS. Our results thus suggest that the inhibition of IDO enhances the suppression of activated HSCs, and therefore co-Treatment with IFN-γ and 1-MT may be applied to ameliorate liver fibrosis.

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