1. Academic Validation
  2. Co-treatment with interferon-γ and 1-methyl tryptophan ameliorates cardiac fibrosis through cardiac myofibroblasts apoptosis

Co-treatment with interferon-γ and 1-methyl tryptophan ameliorates cardiac fibrosis through cardiac myofibroblasts apoptosis

  • Mol Cell Biochem. 2019 Aug;458(1-2):197-205. doi: 10.1007/s11010-019-03542-7.
Jun-Won Lee 1 Ji Eun Oh 2 Ki-Jong Rhee 3 Byung-Su Yoo 4 Young Woo Eom 5 Sang Wook Park 1 Ji Hyun Lee 1 Jung-Woo Son 1 Young Jin Youn 1 Min-Soo Ahn 1 Sung-Gyun Ahn 1 Jang-Young Kim 1 Seung-Hwan Lee 1 Junghan Yoon 1
Affiliations

Affiliations

  • 1 Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, Gangwon-do, 26426, Korea.
  • 2 Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, Gangwon-do, 26426, Korea.
  • 3 Cell Department of Biomedical Laboratory Science, Yonsei University College of Health Sciences, Wonju, Korea.
  • 4 Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, Gangwon-do, 26426, Korea. yubs@yonsei.ac.kr.
  • 5 Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, Gangwon-do, 26426, Korea. yweom@yonsei.ac.kr.
Abstract

Cardiac remodeling characterized by cardiac fibrosis is a pathologic process occurring after acute myocardial infarction. Fibrosis can be ameliorated by interferon-gamma (IFN-γ), which is a soluble cytokine showing various effects such as anti-fibrosis, Apoptosis, anti-proliferation, immunomodulation, and anti-viral activities. However, the role of IFN-γ in cardiac myofibroblasts is not well established. Therefore, we investigated the anti-fibrotic effects of IFN-γ in human cardiac myofibroblasts (hCMs) in vitro and whether indoleamine 2,3-dioxygenase (IDO), induced by IFN-γ and resulting in cell cycle arrest, plays an important role in regulating the biological activity of hCMs. After IFN-γ treatment, cell signaling pathways and DNA contents were analyzed to assess the biological activity of IFN-γ in hCMs. In addition, an IDO Inhibitor (1-methyl tryptophan; 1-MT) was used to assess whether IDO plays a key role in regulating hCMs. IFN-γ significantly inhibited hCM proliferation, and IFN-γ-induced IDO expression caused cell cycle arrest in G0/G1 through tryptophan depletion. Moreover, IFN-γ treatment gradually suppressed the expression of α-smooth muscle actin. When IDO activity was inhibited by 1-MT, marked Apoptosis was observed in hCMs through the induction of interferon regulatory factor, Fas, and Fas ligand. Our results suggest that IFN-γ plays key roles in anti-proliferative and anti-fibrotic activities in hCMs and further induces Apoptosis via IDO inhibition. In conclusion, co-treatment with IFN-γ and 1-MT can ameliorate fibrosis in cardiac myofibroblasts through Apoptosis.

Keywords

Apoptosis; Indoleamine 2,3-dioxygenase; Interferon-gamma; Myofibroblast.

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