Liposomal Targeting of Prednisolone Phosphate to Synovial Lining Macrophages during Experimental Arthritis Inhibits M1 Activation but Does Not Favor M2 Differentiation
SourcePLoS One, 8, 2, (2013), article e54016
Article / Letter to editor
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SubjectNCMLS 1: Infection and autoimmunity N4i 4: Auto-immunity, transplantation and immunotherapy
BACKGROUND: To determine the effects of liposomal targeting of prednisolone phosphate (Lip-PLP) to synovial lining macrophages on M1 and M2 polarization in vitro and during experimental arthritis. MATERIAL AND METHODS: Experimental arthritis (antigen and immune complex induced) was elicited in mice and prednisolone containing liposomes were given systemically. Synovium was investigated using microarray analysis, RT-PCR and histology. Bone-marrow macrophages were stimulated towards M1 using LPS and IFNgamma before treatment by PLP-liposomes. M1 and M2 markers were determined using RT-PCR. RESULTS: Microarray analysis of biopsies of inflamed synovium during antigen induced arthritis (AIA) showed an increased M1 signature characterized by upregulation of IL-1beta, IL-6 and FcgammaRI starting from day 1 and lasting up until day 7 after arthritis induction. The M2 signature remained low throughout the 7 day course of arthritis. Treatment of AIA with intravenously delivered Lip-PLP strongly suppressed joint swelling and synovial infiltration whereas colloidal gold containing liposomes exclusively targeted the macrophages within the inflamed synovial intima layer. studies showed that Lip-PLP phagocytosed by M1 macrophages resulted in a suppression of the M1 phenotype and induction of M2 markers (IL-10, TGF-beta, IL-1RII, CD163, CD206 and Ym1). , Lip-PLP treatment strongly suppressed M1 markers (TNF-alpha, IL-1beta, IL-6, IL-12p40, iNOS, FcgammaRI, Ciita and CD86) after local M1 activation of lining macrophages with LPS and IFN-gamma and during experimental AIA and immune complex arthritis (ICA). In contrast, M2 markers were not significantly upregulated in antigen-induced arthritis and down regulated in immune complex arthritis. CONCLUSION: This study clearly shows that systemic treatment with PLP-liposomes selectively targets synovial lining macrophages and inhibits M1 activation. In contrast to findings, PLP-liposomes do not cause a shift of synovial lining macrophages towards M2.
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