PMID- 22146575
OWN - NLM
STAT- MEDLINE
DCOM- 20121214
LR  - 20240406
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 13
IP  - 6
DP  - 2011
TI  - A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, 
      inverse correlation with disease activity score and suppression of inflammatory 
      cytokine and metalloproteinase release.
PG  - R197
LID - 10.1186/ar3527 [doi]
AB  - INTRODUCTION: The reduction of the inflammatory status represents one of the most 
      important targets in rheumatoid arthritis (RA). A central role of A2A and A3 
      adenosine receptors (ARs) in mechanisms of inflammation has been reported in 
      different pathologies. The primary aim of this study was to investigate the A2A 
      and A3ARs and their involvement in RA progression measured by Disease Activity 
      Score in 28 or 44 joints (DAS28 or DAS). METHODS: ARs were analyzed by saturation 
      binding assays, mRNA and Western blotting analysis in lymphocytes from early and 
      established RA patients. The effect of A2A and A3AR agonists in nuclear factor kB 
      (NF-kB) pathway was evaluated. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta 
      (IL-1beta) and interleukin-6 (IL-6) release was carried out by A2A and A3AR 
      activation. AR pharmacological regulation in matrix metalloproteinase-1 (MMP-1) 
      and metalloproteinase-3 (MMP-3) release was also studied. RESULTS: In lymphocytes 
      obtained from RA patients, A2A and A3ARs were up-regulated if compared with 
      healthy controls. A2A and A3AR activation inhibited the NF-kB pathway and 
      diminished inflammatory cytokines such as TNF-alpha, IL-1beta and IL-6. A2A and A3AR 
      agonists mediated a reduction of MMP-1 and MMP-3 release. A2A and A3AR density 
      inversely correlated with DAS28 and DAS suggesting a direct role of the 
      endogenous activation of these receptors in the control of RA joint inflammation. 
      CONCLUSIONS: Taken together these data demonstrate that the inflammatory and 
      clinical responses in RA are regulated by A2A and A3ARs and support the use of 
      A2A and/or A3AR agonists as novel and effective pharmacological treatment in RA 
      patients.
FAU - Varani, Katia
AU  - Varani K
AD  - Department of Clinical and Experimental Medicine, Pharmacology Unit, University 
      of Ferrara via Fossato di Mortara 17-19, 44121 Ferrara, Italy.
FAU - Padovan, Melissa
AU  - Padovan M
FAU - Vincenzi, Fabrizio
AU  - Vincenzi F
FAU - Targa, Martina
AU  - Targa M
FAU - Trotta, Francesco
AU  - Trotta F
FAU - Govoni, Marcello
AU  - Govoni M
FAU - Borea, Pier Andrea
AU  - Borea PA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111206
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Adenosine A2 Receptor Agonists)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Phenethylamines)
RN  - 0 (Receptor, Adenosine A2A)
RN  - 0 (Receptor, Adenosine A3)
RN  - 120225-54-9 (2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine)
RN  - EC 3.4.- (Metalloproteases)
RN  - K72T3FS567 (Adenosine)
RN  - Z07JR07J6C (2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide)
SB  - IM
MH  - Adenosine/analogs & derivatives/pharmacology
MH  - Adenosine A2 Receptor Agonists/pharmacology
MH  - Aged
MH  - Arthritis, Rheumatoid/*genetics/metabolism/pathology
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Female
MH  - *Gene Expression
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Linear Models
MH  - Lymphocytes/drug effects/metabolism
MH  - Male
MH  - Metalloproteases/metabolism
MH  - Middle Aged
MH  - NF-kappa B/metabolism
MH  - Phenethylamines/pharmacology
MH  - Radioligand Assay
MH  - Receptor, Adenosine A2A/*genetics/metabolism
MH  - Receptor, Adenosine A3/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Severity of Illness Index
MH  - Signal Transduction/drug effects
MH  - Up-Regulation
PMC - PMC3334647
EDAT- 2011/12/08 06:00
MHDA- 2012/12/15 06:00
PMCR- 2011/12/06
CRDT- 2011/12/08 06:00
PHST- 2011/07/28 00:00 [received]
PHST- 2011/10/03 00:00 [revised]
PHST- 2011/12/06 00:00 [accepted]
PHST- 2011/12/08 06:00 [entrez]
PHST- 2011/12/08 06:00 [pubmed]
PHST- 2012/12/15 06:00 [medline]
PHST- 2011/12/06 00:00 [pmc-release]
AID - ar3527 [pii]
AID - 10.1186/ar3527 [doi]
PST - ppublish
SO  - Arthritis Res Ther. 2011;13(6):R197. doi: 10.1186/ar3527. Epub 2011 Dec 6.