Research reportInterferon (IFN)-induced protein 35 (IFI35) negatively regulates IFN-β-phosphorylated STAT1-RIG-I-CXCL10/CCL5 axis in U373MG astrocytoma cells treated with polyinosinic-polycytidylic acid

- Poly IC induced IFI35 in U373MG astrocytoma cells.
- IFN-β is involved in this reaction.
- Knockdown of IFI35 enhanced the poly IC-induced expression of IFN-β, P-STAT1, RIG-I, CXCL10, CCL5.
- IFI35 may inhibits IFN-β-P-STAT1-RIG-I-CXCL10/CCL5 axis.
- IFI35 may constitute a negative feedback loop in poly IC-treated U373MG cells.

Interferon (IFN)-stimulated genes (ISGs) exert multiple functions in immune system. IFN-induced protein 35 (IFI35) is a member of ISGs, and has been suggested to regulate innate immune reaction. However, the physiological functions and pathological roles of IFI35 in the central nervous system are not characterized well. In the present study, we found that the expression of IFI35 was induced by a Toll-like receptor 3 (TLR3) ligand polyinosinic-polycytidylic acid (poly IC) in U373MG human astrocytoma cells. Knockdown of IFI35 using RNA interference resulted in increased expression of IFN-β, phosphorylated STAT1 (P-STAT1), retinoic acid-inducible gene-I (RIG-I), CXCL10 and CCL5 induced by poly IC. Poly IC-induced expression of CXCL10 and CCL5 was decreased by knockdown of RIG-I. These results suggest that IFI35 may negatively regulate the TLR3-IFN-β-P-STAT1-RIG-I-CXCL10/CCL5 axis in U373MG cells, and IFI35 may play a role at least partially in the regulation of innate immune reactions in astrocytes.