Abstract
BackgroundRheumatoid arthritis (RA) is a progressive systemic autoimmune disease that is characterized by infiltration of inflammatory cells into the hyperplastic synovial tissue, resulting in subsequent destruction of adjacent articular cartilage and bone. Methotrexate (MTX), the first conventional disease-modifying antirheumatic drug (DMARD), could alleviate articular damage in RA and is implicated in humoral and cellular immune responses. However, MTX has several side effects, so efficient delivery of low-dose MTX is important.MethodsTo investigate the efficacy of MTX-loaded nanoparticles (MTX-NPs) against experimental model of RA, free MTX or MTX-NPs were administered as subcutaneous route to mice with collagen-induced arthritis (CIA) at 3 weeks after CII immunization. The levels of inflammatory factors in tissues were determined by immunohistochemistry, confocal microscopy, real-time PCR, and flow cytometry.ResultsMTX-NPs ameliorated arthritic severity and joint destruction in collagen-induced arthritis (CIA) mice compared to free MTX-treated CIA mice. The levels of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, and vascular endothelial growth factor, were reduced in MTX-NPs-treated mice. Number of CD4 + IL-17 + cells decreased whereas the number of CD4 + CD25 + Foxp3 + cells increased in spleens from MTX- NPs-treated CIA mice compared to MTX-treated CIA mice. The frequency of CD19 + CD25 + Foxp3 + regulatory B cells increased in ex vivo splenocytes from MTX-loaded NPs-treated CIA mice compared to MTX-treated CIA mice.ConclusionThe results suggest that MTX-loaded NPs have therapeutic potential for RA.
Highlights
Rheumatoid arthritis (RA) is a progressive systemic autoimmune disease that is characterized by infiltra‐ tion of inflammatory cells into the hyperplastic synovial tissue, resulting in subsequent destruction of adjacent articu‐ lar cartilage and bone
MTX‐NPs increase regulatory B cells in vivo To evaluate whether MTX-loaded nanoparticles (MTX-NPs) act on B-cell responses in vivo, we examined the number of ex vivo CD19 + B220 + GL-7 + Fas + germinal center (GC) B cells and CD19 + CD5 + CD1d + IL-10 + regulatory B (Breg) cells in splenocytes from collagen-induced arthritis (CIA) mice injected with MTXNPs by flow cytometry
In summary, our study showed a therapeutic efficacy of MTX-NPs in mice with CIA
Summary
Rheumatoid arthritis (RA) is a progressive systemic autoimmune disease that is characterized by infiltra‐ tion of inflammatory cells into the hyperplastic synovial tissue, resulting in subsequent destruction of adjacent articu‐ lar cartilage and bone. Rheumatoid arthritis (RA) is a progressive autoimmune disease characterized by synovial inflammation, hyperplasia, and formation of rheumatoid pannus, resulting in destruction of the adjacent articular cartilage and bone structure. In RA synovium, IL-17-producing cells were observed in the T cell-rich area and IL-17 contributes to increased production of IL-6 and leukemia inhibitory factor. It has synergistic effects with IL-1β or TNF-α on inflammation [9,10,11]. B cells act as antigen-presenting cells for autoreactive T cells [13]
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