The PI3K-NF-kappaB signal transduction pathway is involved in mediating the anti-inflammatory effect of IB-MECA in adjuvant-induced arthritis

Arthritis Research & Therapy
P FishmanEhud Baharav

Abstract

The anti-inflammatory effect of adenosine was previously found to be mediated via activation of the A3 adenosine receptor (A3AR). The aim of the present study was to decipher the molecular mechanism involved with the inhibitory effect of IB-MECA, an A3AR agonist, on adjuvant-induced arthritis. The adjuvant-induced arthritis rats responded to IB-MECA treatment with a decrease in the clinical score and the pathological score of the disease. The response to IB-MECA was neutralized by the antagonist MRS 1220, confirming that the efficacy of the synthetic agonist was A3AR mediated. The A3AR protein expression level was highly expressed in the synovia, in the peripheral blood mononuclear cells and in the drain lymph node (DLN) tissues of adjuvant-induced arthritis rats in comparison with naïve animals. Downregulation of A3AR expression was noted upon treatment with IB-MECA. Analysis of synovia and DLN protein extracts revealed a decreased expression level of PI3K, PKB/Akt, IKK, NF-kappaB and tumor necrosis factor alpha, known to affect survival and apoptosis of inflammatory cells, whereas the caspase-3 level was upregulated.Taken together, high A3AR expression is found in the synovia, in the immune cells in the DLN and in peripheral ...Continue Reading

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Citations

Jun 12, 2012·Arthritis Research & Therapy·Lisa K StampPaul A Hessian
Sep 3, 2011·International Journal of Molecular Medicine·Sara Bar-YehudaPnina Fishman
Feb 22, 2012·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Kazuhiko HarutaYoshinari Takasaki
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Apr 5, 2011·Expert Opinion on Investigational Drugs·Balázs KoscsóGyörgy Haskó
Oct 10, 2007·Expert Opinion on Investigational Drugs·Sara Bar-YehudaPnina Fishman
Oct 25, 2011·Expert Opinion on Investigational Drugs·Stefania GessiPier Andrea Borea
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Methods Mentioned

BETA
xenograft
protein assay

Software Mentioned

SAS

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