The anti-inflammatory target A₃ adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease

The Gi protein associated A₃ adenosine receptor (A₃AR) was recently defined as a novel anti-inflammatory target. The aim of this study was to look at A₃AR expression levels in peripheral blood mononuclear cells (PBMCs) of patients with autoimmune inflammatory diseases and to explore transcription factors involved receptor expression. Over-expression of A₃AR was found in PBMCs derived from patients with rheumatoid arthritis (RA), psoriasis and Crohn's disease compared with PBMCs from healthy subjects. Bioinformatics analysis demonstrated the presence of DNA binding sites for nuclear factor-κB (NF-κB) and cyclic AMP-responsive element binding protein (CREB) in the A₃AR gene promoter. Up-regulation of NF-κB and CREB was found in the PBMCs from patients with RA, psoriasis and Crohn's disease. The PI3K-PKB/Akt signaling pathway, known to regulate both the NF-κB and CREB, was also up-regulated in the patients' PBMCs. Taken together, NF-κB and CREB are involved with the over-expression of A₃AR in patients with autoimmune inflammatory diseases. The receptor may be considered as a specific target to combat inflammation.