Back to Search
Start Over
Co-treatment with interferon-γ and 1-methyl tryptophan ameliorates cardiac fibrosis through cardiac myofibroblasts apoptosis
- Source :
- Molecular and Cellular Biochemistry
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
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.
- Subjects :
- 0301 basic medicine
Indoleamine 2,3-dioxygenase
Cardiac fibrosis
medicine.medical_treatment
Clinical Biochemistry
Myocardial Infarction
Muscle Proteins
Apoptosis
Article
Fas ligand
Interferon-gamma
03 medical and health sciences
0302 clinical medicine
Fibrosis
Autophagy
medicine
Humans
Interferon gamma
Myofibroblasts
Molecular Biology
Myofibroblast
Chemistry
Myocardium
Tryptophan
Cell Cycle Checkpoints
Cell Biology
General Medicine
medicine.disease
030104 developmental biology
Cytokine
Gene Expression Regulation
030220 oncology & carcinogenesis
Cancer research
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 15734919 and 03008177
- Volume :
- 458
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biochemistry
- Accession number :
- edsair.doi.dedup.....c58bfed173d2a96ad990184e42698ef7