The anti-inflammatory target A(3) adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease.
The Gi protein associated A(3) adenosine receptor (A(3)AR) was recently defined as a novel anti-inflammatory target. The aim of this study was to look at A(3)AR 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 A(3)AR 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-kappaB (NF-kappaB) and cyclic AMP-responsive element binding protein (CREB) in the A(3)AR gene promoter. Up-regulation of NF-kappaB 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-kappaB and CREB, was also up-regulated in the patients' PBMCs. Taken together, NF-kappaB and CREB are involved with the over-expression of A(3)AR in patients with autoimmune inflammatory diseases. The receptor may be considered as a specific target to combat inflammation.
Ochaion
A
A
Can-Fite BioPharma Ltd., Kiryat-Matalon, Petah-Tikva, Israel.
Bar-Yehuda
S
S
Cohen
S
S
Barer
F
F
Patoka
R
R
Amital
H
H
Reitblat
T
T
Reitblat
A
A
Ophir
J
J
Konfino
I
I
Chowers
Y
Y
Ben-Horin
S
S
Fishman
P
P
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002478:Cells, Cultured; D003424:Crohn Disease / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D043684:Receptor, Adenosine A3 / Q000096:biosynthesis* / Q000235:genetics; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation; D000097868:Polo-like Kinases
D017362:Cyclic AMP Response Element-Binding Protein; D051550:I-kappa B Kinase; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D043684:Receptor, Adenosine A3; D025521:Tumor Suppressor Proteins; C115163:CREB1 protein, human; C486256:PLK3 protein, human; D000097868:Polo-like Kinases