Rig-I is involved in inflammation through the IPS-1/TRAF 6 pathway in astrocytes under chemical hypoxia

• Published in: Neuroscience letters Vol. 672; p. 46
• Main Authors: Li, Lei, Yang, Rongli, Feng, Meijiang, Guo, YiChen, Wang, YuXuan, Guo, Jun, Lu, Xiang
• Format: Journal Article
• Language: English
• Published: Ireland 13.04.2018
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Astrocytes - drug effects; Astrocytes - metabolism; Cell Hypoxia - drug effects; Cell Hypoxia - physiology; Cell Line, Tumor; Cobalt - pharmacology; DEAD Box Protein 58 - metabolism; Humans; Inflammation - metabolism; Receptors, Immunologic; Signal Transduction - drug effects; TNF Receptor-Associated Factor 6 - metabolism; Up-Regulation; Chemical hypoxia; TRAF6; Neuroinflammation; RIG-I; IPS-1
• ISSN: 1872-7972

The retinoic acid-inducible gene I (RIG-I) is a crucial cytoplasmic pathogen recognition receptor involved in neuroinflammation in degenerative diseases. In the present study, in vitro human astrocytes were subjected to a chemical hypoxia model using cobalt chloride pretreatment. Chemical hypoxia induces the up-regulation of RIG-I in astrocytes and results in the expression of inflammatory cytokines IL-1β, IL-6, and TNF-α in an NF-κB dependent manner. Elevated RIG-I modulates the interaction of interferon-β promoter stimulator-1 (IPS-1) and TNF receptor-associated factor 6 (TRAF6) following chemical hypoxia. Inhibition of IPS-1 or TRAF6 suppresses RIG-I-induced NF-κB activation and inflammatory cytokines in response to chemical hypoxia. These data suggest that chemical hypoxia leads to RIG-I activation and the expression of inflammatory cytokines through the NF-κB pathway. Blocking IPS-1/TRAF6 pathway relieves RIG-I-induced neuroinflammation in astrocytes subjected to hypoxia.