Conclusions
A(2A)R activation suppressed inflammation in the kidneys of MRL/lpr mice and can be considered as a novel therapeutic approach for human lupus nephritis.
Methods
MRL/lpr mice were given a selective A(2A)R agonist, CGS21680 (0.4 mg/kg per day, i.p.) while control mice received saline only. After 8 weeks of treatment, mice were sacrificed for assessment of functional and histological parameters as well as inflammatory infiltration in the kidneys. MCP-1, IFN-γ, MHC-II and A(2A)R mRNA expression was evaluated by RT-PCR. Expression of A(2A)R and nuclear NFκB p65 protein was determined by Western blot analysis. Levels of anti-dsDNA antibody and IFN-γ were measured by ELISA.
Objective
Adenosine is considered as a potent endogenous anti-inflammatory and immunosuppressive molecule. We examined the roles of A2A-adenosine receptor (A(2A)R) in the progression of lupus nephritis.
Results
CGS21680 treatment resulted in significant decrease in proteinuria, blood urea and creatinine as well as improvement in renal histology. Renal macrophage and T-cell infiltration were significantly attenuated in association with suppressed expression of MCP-1, IFN-γ and MHC-II. CGS21680 treatment reduced the level of serum anti-dsDNA and renal immune complex deposition. CGS21680 inhibited the activation of NFκB and suppressed the expression of IFN-γ, MCP-1 and MHC-II in MRL/lpr splenocytes. Conclusions: A(2A)R activation suppressed inflammation in the kidneys of MRL/lpr mice and can be considered as a novel therapeutic approach for human lupus nephritis.