Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis
Abstract
IFNs are a family of cytokines with pleiotropic biological effects mediated by scores of responsive genes. IFNs were the first human proteins to be effective in cancer therapy and were among the first recombinant DNA products to be used clinically. Both quality and quantity of life has been improved in response to IFNs in various malignancies. Despite its beneficial effects, unraveling the mechanisms of the anti-tumor effects of IFN has proven to be a complex task. IFNs may mediate anti-tumor effects either indirectly by modulating immunomodulatory and anti-angiogenic responses or by directly affecting proliferation or cellular differentiation of tumor cells. Both direct or indirect effects of IFNs result from induction of a subset of genes, called IFN stimulated genes (ISGs). In addition to the ISGs implicated in anti-viral, anti-angiogenic, immunomodulatory and cell cycle inhibitory effects, oligonucleotide microarray studies have identified ISGs with apoptotic functions. These include TNF-alpha related apoptosis inducing ligand (TRAIL/Apo2L), Fas/FasL, XIAP associated factor-1 (XAF-1), caspase-4, caspase-8, dsRNA activated protein kinase (PKR), 2'5'A oligoadenylate synthetase (OAS), death activating protein kinases (DAP kinase), phospholipid scramblase, galectin 9, IFN regulatory factors (IRFs), promyelocytic leukemia gene (PML) and regulators of IFN induced death (RIDs). In vitro IFN-alpha, IFN-beta and IFN-gamma induced apoptosis in multiple cell lines of varied histologies. This review will emphasize possible mechanisms and the role of ISGs involved in mediating apoptotic function of IFNs.
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Inflammatory cytokines influence neuronal development and apoptosis, and both stress and inflammatory cytokine activity may adversely influence neurogenesis and neuroplasticity.
“Inflammatory cytokines have repeatedly been observed to influence both neuronal development and apoptosis (Chawla-Sarkar et al., 2003, Hayley et al., 2005) (Mehler and Kessler, 1997, Zhao and Schwartz, 1998), (Peng et al., 2008, Anisman, 2009, Koo et al., 2010b). In fact, both stress and subsequent inflammatory cytokine activity may adversely influence neurogenesis and neuroplasticity (Patel et al”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Chawla-Sarkar et al., 2003
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- Authors
- Chawla-Sarkar, M., Lindner, D. J., Liu, Y.-F., Williams, B. R., Sen, G. C., Silverman, R. H., & Borden, E. C.
- Affiliations
- Cleveland Clinic (US)
- ORCID
- Williams, B. R.
- Venue
- Apoptosis
- Published
- 2003-06
- Volume
- 8
- Issue
- 3
- Pages
- 237-249
- ISSN
- 1360-8185 (ISSN-L)
- 1573-675X
- OpenAlex
- W65867874
- Cited by
- 829
- References
- 103
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 31 · 2023: 32 · 2022: 35 · 2021: 33 · 2020: 29 · 2019: 33 · 2018: 34 · 2017: 29 · 2016: 34 · 2015: 45 · 2014: 29 · 2013: 50 · 2012: 41
- FWCI
- 14.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- APOPTOSIS (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA44059, R01 CA 90914, R01CA044059, R01CA090914)
- National Institute of Allergy and Infectious Diseases (AI 34039)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- interferon, interferon-stimulated genes, anti-tumor effect, TRAIL, Fas/FasL, caspase-4, caspase-8, PKR, 2',5'-oligoadenylate synthetase, DAP kinase, galectin-9, PML, interferon-alpha, interferon-beta, interferon-gamma, cancer cell death
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Gene Expression Regulation, Humans, Interferons, Receptors, Cell Surface, Signal Transduction, Apoptosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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