title: Adenosine 2A receptor is protective against renal injury in MRL/lpr mice.
abstract: 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.
  
  
  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.
  
  
  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.
authors.affiliation: Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: N
authors.initials: N
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Huang
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Tan
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Yu
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D008181:Lupus Nephritis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010627:Phenethylamines / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D058908:Adenosine A2 Receptor Agonists; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D012313:RNA; D000241:Adenosine