Rheumatoidarthritis (RA) is an
autoimmune disease characterized by uncontrolled joint
inflammation and damage to bone and cartilage. B cells are known to play a crucial role in the pathogenesis and development of
arthritis. Previous studies have found that B cells may be a potential target for treating RA.
Rituximab, a
monoclonal antibody targeting B cells, has induced long-term clinical responses in RA.
Collagen-induced arthritis (CIA) mouse model is a widely studied autoimmune model of RA. CIA mouse model was used to investigate the effect of
rituximab on the RA severity in the mice. Following induction of CIA, animals were treated with
rituximab (250 mg/kg/week) intraperitoneally on the days 28, 35, 42, 49, 56, and 63 after
collagen induction. We investigated the effect of
rituximab on NF-κB p65, IκBα,
GM-CSF, MCP-1, iNOS, TNF-α, and IL-6 cells in splenic CD19+ and CD45R+ B cells using flow cytometry. We also assessed the effect of
rituximab on NF-κB p65,
GM-CSF, IκBα, MCP-1, iNOS, TNF-α, and
IL-6 at
mRNA levels using RT-PCR analyses of knee tissues.
Rituximab treatment significantly decreased CD19+NF-κB p65+, CD45R+NF-κB p65+, CD19+GM-CSF+, CD45R+GM-CSF+, CD19+MCP-1+, CD45R+MCP-1+, CD19+TNF-α+, CD45R+TNF-α+, CD19+iNOS+, CD45R+iNOS+, CD19+IL-6+, and CD45R+IL-6+, and increased CD45R+IκBα+ in spleen cells of CIA mice. We further observed that
rituximab treatment downregulated NF-κB p65,
GM-CSF, MCP-1, iNOS, TNF-α, and
IL-6, whereas it upregulated IκBα,
mRNA level. All these findings suggest that
rituximab may be a novel therapeutic target for the treatment of RA.