Fluoxetine a novel anti-hepatitis C virus agent via ROS-, JNK-, and PPARβ/γ-dependent pathways

Kung Chia Young, Chyi Huey Bai, Hui Chen Su, Pei Ju Tsai, Chien Yu Pu, Chao Sheng Liao, Yu Min Lin, Hsin Wen Lai, Lee Won Chong, Yau Sheng Tsai, Chiung Wen Tsao

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

More than 20% of chronic hepatitis C (CHC) patients receiving interferon-alpha (IFN-α)-based anti-hepatitis C virus (HCV) therapy experienced significant depression, which was relieved by treatment with fluoxetine. However, whether and how fluoxetine affected directly the anti-HCV therapy remained unclear. Here, we demonstrated that fluoxetine inhibited HCV infection and blocked the production of reactive oxygen species (ROS) and lipid accumulation in Huh7.5 cells. Fluoxetine facilitated the IFN-α-mediated antiviral actions via activations of signal transducer and activator of transcription (STAT)-1 and c-Jun amino-terminal kinases (JNK). Alternatively, fluoxetine elevated peroxisome proliferator-activated receptor (PPAR) response element activity under HCV infection. The inhibitory effects of fluoxetine on HCV infection and lipid accumulation, but not production of ROS, were partially reversed by the PPAR-β, -γ, and JNK antagonists. Furthermore, fluoxetine intervention to the IFN-α-2b regimen facilitated to reduce HCV titer and alanine transaminase level for CHC patients. Therefore, fluoxetine intervention to the IFN-α-2b regimen improved the efficacy of anti-HCV treatment, which might be related to blockades of ROS generation and lipid accumulation and activation of host antiviral JNK/STAT-1 and PPARβ/γ signals.

Original languageEnglish
Pages (from-to)158-167
Number of pages10
JournalAntiviral Research
Volume110
DOIs
Publication statusPublished - 2014

Fingerprint

Peroxisome Proliferator-Activated Receptors
Fluoxetine
Hepacivirus
Reactive Oxygen Species
Phosphotransferases
interferon alfa-2b
Virus Diseases
STAT1 Transcription Factor
Chronic Hepatitis C
Lipids
Interferon-alpha
Antiviral Agents
JNK Mitogen-Activated Protein Kinases
Response Elements
Therapeutics
Viral Load
Alanine Transaminase

Keywords

  • Fluoxetine
  • Hepatitis C virus
  • Interferon-α
  • JNK
  • PPAR-β/γ
  • STAT-1

ASJC Scopus subject areas

  • Virology
  • Pharmacology
  • Medicine(all)

Cite this

Fluoxetine a novel anti-hepatitis C virus agent via ROS-, JNK-, and PPARβ/γ-dependent pathways. / Young, Kung Chia; Bai, Chyi Huey; Su, Hui Chen; Tsai, Pei Ju; Pu, Chien Yu; Liao, Chao Sheng; Lin, Yu Min; Lai, Hsin Wen; Chong, Lee Won; Tsai, Yau Sheng; Tsao, Chiung Wen.

In: Antiviral Research, Vol. 110, 2014, p. 158-167.

Research output: Contribution to journalArticle

Young, KC, Bai, CH, Su, HC, Tsai, PJ, Pu, CY, Liao, CS, Lin, YM, Lai, HW, Chong, LW, Tsai, YS & Tsao, CW 2014, 'Fluoxetine a novel anti-hepatitis C virus agent via ROS-, JNK-, and PPARβ/γ-dependent pathways', Antiviral Research, vol. 110, pp. 158-167. https://doi.org/10.1016/j.antiviral.2014.08.002
Young, Kung Chia ; Bai, Chyi Huey ; Su, Hui Chen ; Tsai, Pei Ju ; Pu, Chien Yu ; Liao, Chao Sheng ; Lin, Yu Min ; Lai, Hsin Wen ; Chong, Lee Won ; Tsai, Yau Sheng ; Tsao, Chiung Wen. / Fluoxetine a novel anti-hepatitis C virus agent via ROS-, JNK-, and PPARβ/γ-dependent pathways. In: Antiviral Research. 2014 ; Vol. 110. pp. 158-167.
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