Biochemical and Biophysical Research Communications, Vol.508, No.3, 894-901, 2019
Eosinophils attenuate arthritis by inducing M2 macrophage polarization via inhibiting the I kappa B/P38 MAPK signaling pathway
Rheumatoid arthritis (RA) represents a type of autoimmune disease that mainly affect the joints due to persistent synovitis. Eosinophils were Th2 effector cells that have been shown to have anti-inflammatory role recently. In this study, we aimed to investigate the effects of eosinophils transfer on arthritis and underlying mechanisms. DBA/1 mice were induced with collagen-induced arthritis (CIA) and treated with purified eosinophils at different time points. We showed that eosinophils transfer attenuated arthritis in CIA mice. Meanwhile, TNF-alpha, IL-6, IL-12 and iNOS levels were decreased whereas TGF-beta, IL-10, IL-13 and Arg1 levels were increased after eosinophil transfer. In vitro stimulation of bone marrow-derived macrophage (BMDM) with LPS and IFN-gamma induced high expression of CD68, iNOS, TNF-alpha, IL-6, and IL-12, while treatment with eosinophils downregulated their expression levels. Furthermore, high levels of p-I kappa B and p-P38 expression in BMDM induced by LPS and IFN-gamma could be suppressed by eosinophil treatment, and a P38 or I kappa B inhibitor accelerated the effect of eosinophils on macrophage polarization. Our results demonstrate that eosinophils exert anti-inflammatory effects in arthritis by inducing M2 macrophage polarization via inhibiting the I kappa B/P38 MAPK signaling pathway. (C) 2018 Elsevier Inc. All rights reserved.
Keywords:Eosinophils;Macrophage polarization;I kappa B/p38 MAPK signaling pathway;Rheumatoid arthritis