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The Anti-Inflammatory Effects of Interferon Tau by Suppressing NF-κB/MMP9 in Macrophages Stimulated with Staphylococcus aureus
The Journal of Interferon & Cytokine Research, 2016, 36(8): 516-524.
The Anti-Inflammatory Effects of Interferon Tau by Suppressing NF-κB/MMP9 in Macrophages Stimulated with Staphylococcus aureus
Authors: Zhao G, Wu H, Jiang K, et al.
PMID: 27142785
PMID: 27142785
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. aureuswere 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.