The Anti-Inflammatory Effects of Interferon Tau by Suppressing NF-κB/MMP9 in Macrophages Stimulated with Staphylococcus aureus.

Abstract

Previous studies have reported that interferon tau (IFNT) significantly mitigates tissue inflammation. However, this effect and its regulating pathways have not been reported for Staphylococcus aureus-induced inflammation. In this study, RAW 264.7 cells stimulated with S. aureus were used to identify the anti-inflammatory effects and mechanism of IFNT. First, IFNT was found to be noncytotoxic to macrophages treated with the high dose of 200 ng/mL IFNT. ELISA and qPCR revealed that IFNT decreased the expression of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. TLR2, which is involved in the immune response during S. aureus infection, directly affected NF-κB pathway activation and was also downregulated by IFNT. Subsequent Western blotting showed that the phosphorylation of IκBα and NF-κB p65 was inhibited by IFNT. Therefore, although the MMP9 levels were significantly downregulated in a dose-dependent manner by IFNT, little change in MMP2 was observed in S. aureus-stimulated RAW 264.7 cells. Furthermore, PDTC, an inhibitor of NF-κB, also significantly decreased MMP9 levels by inhibiting NF-κB p65 activation. All of these findings strongly suggested that IFNT suppresses the NF-κB/MMP9 signal transduction pathway and subsequently exerts its anti-inflammatory effects in S. aureus-stimulated RAW 264.7 cells.