Rig-I is involved in inflammation through the IPS-1/TRAF6 pathway in astrocytes under chemical hypoxia.

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.