Overexpression of A3 adenosine receptor in peripheral blood mononuclear cells in rheumatoid arthritis: involvement of nuclear factor-kappaB in mediating receptor level.

Abstract

OBJECTIVE:

A3 adenosine receptor (A3AR) upregulation has been found in cells of synovial tissue and in peripheral blood mononuclear cells (PBMC) of rats with adjuvant-induced arthritis. We investigated A3AR levels in PBMC of patients with rheumatoid arthritis (RA) and in mitogen-activated PBMC from healthy subjects. We examined the role of nuclear factor-kappaB (NF-kappaB), a transcription factor present in the A3AR promoter, in mediating receptor upregulation.

METHODS:

A3AR and NF-kappaB protein levels were evaluated in PBMC of RA patients (n = 23) and healthy subjects by Western blot. A3AR and NF-kappaB levels were also analyzed in phytohemagglutinin (PHA) and lipopolysaccharide (LPS)-stimulated PBMC in the presence and absence of antibodies against interleukin 2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha). Reverse transcription-polymerase chain reaction was performed in PHA-stimulated PBMC of healthy subjects to determine A3AR expression.

RESULTS:

A3AR was overexpressed in PBMC of RA patients compared to healthy subjects and was directly correlated to an increase in NF-kappaB. Similar findings were observed in PHA and LPS-stimulated PBMC from healthy subjects. Antibodies against IL-2 or TNF-alpha prevented the increase in A3AR and NF-kappaB expression.

CONCLUSION:

Overexpression of A3AR was found in PBMC of RA patients. Receptor upregulation was induced by inflammatory cytokines controlling the expression of the A3AR transcription factor NF-kappaB.

• Authors: Lea Madi, Shira Cohen, Avivit Ochayin, Sara Bar-Yehuda, Faina Barer, Pnina Fishman
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 34 Issue 1 Pg. 20-6 (Jan 2007) ISSN: 0315-162X [Print] Canada
• PMID: 17216675 (Publication Type: Journal Article)

Chemical References

• Interleukin-2
• Mitogens
• NF-kappa B
• Receptor, Adenosine A3
• Tumor Necrosis Factor-alpha
• N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Arthritis, Rheumatoid (blood, metabolism)
• Gene Expression Regulation
• Humans
• Interleukin-2 (antagonists & inhibitors)
• Leukocytes, Mononuclear (metabolism, pathology)
• Middle Aged
• Mitogens (physiology)
• NF-kappa B (physiology)
• Promoter Regions, Genetic (genetics, physiology)
• Receptor, Adenosine A3 (blood, metabolism)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)