Abstract
Paeoniflorin-6’-O-benzene sulfonate (CP-25) is a modified paeoniflorin, which is the main bioactive component of total glucosides of peony. This study evaluated the anti-inflammatory and immunoregulatory effects of CP-25 in mice with collagen-induced arthritis (CIA) and the potential mechanisms underlying these effects. After the onset of CIA, mice were given CP-25 (17.5, 35, or 70 mg/kg) or methotrexate (MTX, 2.0 mg/kg). The arthritis index, swollen joint count, and joint and spleen histopathology were evaluated. T and B cell subsets were assayed using flow cytometry, while the proliferation of these cells and fibroblast-like synoviocytes (FLSs) were evaluated using the Cell Counting Kit-8. β2-adrenoceptor (β2-AR) expression was assayed using flow cytometry, immunohistochemistry, and western blotting. FLS migration and invasion were assayed using Transwells. CP-25 (35 or 70 mg/kg) attenuated the arthritis index and swollen joint count, alleviated joint and spleen histopathology, suppressed excessive T cell activation, and attenuated humoral immunity in CIA mice. CP-25 increased β2-AR expression on T cells, B cells, dendritic cells, and the synovium in CIA mice. CP-25 up-regulated the β2-AR agonist response and attenuated FLS activation; these effects may reflect CP-25-mediated reduction of β2-AR desensitization due to down-regulation of membrane G protein-coupled receptor kinase 2 expression. These results suggest that CP-25 suppressed immune responses and synovium inflammation in mice with CIA, effects that were associated with reduced β2-AR desensitization and the promotion of β2-AR signaling.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by immoderate immune responses to self-antigens and synovium inflammation, which leads to the destruction of the joints (Pablos and Cañete, 2013; Rodeghero et al, 2013)
The present study evaluated the effects of CP-25 on T cell-dependent immune responses and synovium inflammation in mice with collagen-induced arthritis (CIA), and investigated the potential mechanisms involved in the anti-inflammatory and immunoregulatory effects of this compound, with a focus on β2-AR signaling
The white pulp of the spleen is filled with lymphocytes and is the site where T cells and B cells undergo activation, proliferation, and differentiation; lymphoid white pulp hyperplasia was the main damage observed in the spleen of CIA mice
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by immoderate immune responses to self-antigens and synovium inflammation, which leads to the destruction of the joints (Pablos and Cañete, 2013; Rodeghero et al, 2013). In addition to its involvement in autoimmune diseases, the T cell-dependent immune response is essential for host defense against bacterial and viral infections (Boitard, 1992; Goodnow, 1997). During this response, activated immune cells interact each other, infiltrate in the synovium, and result in chronic synovium inflammation and bone erosion in RA. Our previous studies showed that CP-25, as well as Pae and TGP, significantly inhibited the progression of experimental arthritis in rats by reducing inflammation, the immune response, and bone damage (Zheng and Wei, 2005; Zhu et al, 2005; Chang et al, 2016). Our previous studies suggested that the anti-inflammatory and immunoregulatory activities of CP25 may reflect its effects on G protein-coupled receptor (GPCR) signaling; this includes regulation of prostaglandin E2 receptors, including EP2 and EP4 (Xu et al, 2007; Chang et al, 2009, 2011b), G proteins (Jia et al, 2014), β-arrestin 2, and G protein-coupled receptor kinase 2 (GRK2) (Wang et al, 2011; Chen et al, 2012; Wu et al, 2012)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
