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

Jun Won Lee, Ji Eun Oh, Ki Jong Rhee, Byung Su Yoo, Young Woo Eom, Sang Wook Park, Ji Hyun Lee, Jung Woo Son, Young Jin Youn, Min Soo Ahn, Sung Gyun Ahn, Jang Young Kim, Seung Hwan Lee, Junghan Yoon

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)197-205
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume458
Issue number1-2
DOIs
Publication statusPublished - 2019 Aug 15

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Co-treatment with interferon-γ and 1-methyl tryptophan ameliorates cardiac fibrosis through cardiac myofibroblasts apoptosis'. Together they form a unique fingerprint.

  • Cite this