Aims: Adenosine A(2A) and A(2B) receptor subtypes have both been implicated in the modulation of inflammation. We examined adenosine A(2A) and A(2B) receptor expression, signaling pathways and the effect of adenosine A(2A) and A(2B) receptor activation on the uropathogenic Escherichia coli (UPEC)-stimulated IL-8 response in human uroepithelial cells (UROtsa). Methods: Receptor expression was examined by RT-PCR and Western blot, and IL-8 production, intracellular cAMP levels and phosphoproteins were measured by ELISA, EIA and multiplex immunoassay, respectively. Results: The adenosine A(1), A(2A) and A(2B) receptor subtypes were detected in UROtsa cells. The adenosine A(2A) receptor agonist CGS 21680 did not stimulate cAMP production but CREB phosphorylation was slightly increased. The adenosine A(2) receptor agonist CPCA induced a pronounced cAMP and CREB response. Furthermore, CGS 21680 but not CPCA decreased ERK 1/2 and STAT3 phosphorylation. UPEC infection stimulated the host IL-8 production but CPCA or CGS 21680 did not affect UPEC-evoked IL-8 production. Conclusions: Our data identified differences in signaling pathways evoked by adenosine A(2A) and A(2B) receptor activation. Activation of the adenosine A(2A) receptor inhibited STAT3 and ERK 1/2 phosphorylation, while the cAMP-CREB pathway was induced by adenosine A(2B) receptor activation. No anti-or proinflammatory effects were found for uroepithelial adenosine A(2A) or A(2B) receptors. Copyright (C) 2010 S. Karger AG, Basel