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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
Published on: October 28, 2019
Type I interferons induce autophagy in certain human cancer cell lines
Hana Schmeisser1, Samuel B Fey, Julie Horowitz
1National Institutes of Health, National Institute of Allergy and Infectious Disease, Cytokine Biology Section, Bethesda, MD, USA.
Type I interferons (IFNs) induce autophagy, a cellular recycling process, in various human cell lines. This novel function of Type I IFNs was confirmed through increased autophagy markers and autophagosome presence.
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- Autophagy is a fundamental cellular recycling process conserved across species.
- Type I interferons (IFNs) are known for their antiviral, antiproliferative, proapoptotic, and immunomodulatory functions.
- Previous research has identified various stimuli that can induce autophagy, but the role of Type I IFNs was not well-established.
Purpose of the Study:
- To investigate whether Type I IFNs can induce autophagy in human cell lines.
- To elucidate the molecular mechanisms underlying IFN-induced autophagy.
Main Methods:
- Treatment of multiple human cell lines (Daudi B, HeLa S3, MDA-MB-231, T98G, A549) with Type I IFNs (IFNA2c, IFNB).
- Assessment of autophagy markers (MAP1LC3-II, ATG12-ATG5 complexes, SQSTM1) via Western blotting.
- Confirmation of autophagosomes using electron microscopy.
- Analysis of signaling pathways including MTORC1 and PI3K-AKT.
Main Results:
- Type I IFNs (IFNA2c, IFNB) induced autophagy in Daudi B cells within 24 hours, evidenced by increased MAP1LC3-II and ATG12-ATG5, and decreased SQSTM1.
- Increased MAP1LC3-II was observed in HeLa S3, MDA-MB-231, T98G, and A549 cells 48 hours post-IFNA2c treatment.
- Electron microscopy confirmed the presence of autophagosomes.
- IFN-induced autophagy correlated with MTORC1 inhibition, reduced cancer cell proliferation, and cell cycle alterations.
- Blocking MTOR or PI3K-AKT signaling enhanced IFN-induced autophagy, suggesting pathway modulation.
Conclusions:
- Type I IFNs represent a novel inducer of autophagy in diverse human cell lines.
- The PI3K-AKT-MTORC1 signaling pathway plays a role in modulating IFN-induced autophagy.
- This finding expands the known functions of Type I IFNs in cellular processes.
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