Effects of adenosine A(2A) and A(2B) receptor activation on signaling pathways and cytokine production in human uroepithelial cells.
OBJECTIVE
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.
Säve
Susanne
S
School of Natural Sciences, Linnaeus University, Kalmar, Sweden.
Persson
Katarina
K
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D056689:Uropathogenic Escherichia coli / Q000276:immunology; D019459:Urothelium / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology
D058908:Adenosine A2 Receptor Agonists; D016207:Cytokines; D016209:Interleukin-8; D010627:Phenethylamines; D010750:Phosphoproteins; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C024311:N-cyclopropyl adenosine-5'-carboxamide; D000242:Cyclic AMP; D000241:Adenosine