IDO1 and TGF-β Mediate Protective Effects of IFN-α in Antigen-Induced Arthritis.

ABSTRACT: IFN-α prevents Ag-induced arthritis (AIA), and in this study we investigated the role of IDO1 and TGF-β signaling for this anti-inflammatory property of IFN-α. Arthritis was induced by methylated BSA (mBSA) in mBSA-sensitized wild-type (WT), Ido1^-/-, or Ifnar^-/- mice, treated or not with IFN-α or the IDO1 product kynurenine (Kyn). Enzymatic IDO1 activity, TGF-β, and plasmacytoid dendritic cells (pDC) were neutralized by 1-methyltryptophan and Abs against TGF-β and pDC, respectively. IDO1 expression was determined by RT-PCR, Western blot, and FACS, and enzymatic activity by HPLC. Proliferation was measured by ³H-thymidine incorporation and TGF-β by RT-PCR and ELISA. WT but not Ido1^-/- mice were protected from AIA by IFN-α, and Kyn, the main IDO1 p

SUBMITTER: Chalise JP 

PROVIDER: S-EPMC5055200 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature