IL-6 expression induced by adenosine A 2b receptor stimulation in U373 MG cells depends on p38 mitogen activated kinase and protein kinase C

Abstract

Adenosine binds to a class of G-protein coupled receptors, which are further distinguished as A 1, A 2a, A 2b and A 3 adenosine receptors. As we have shown earlier, the stable adenosine analogue NECA ( N6-( R)-phenylisopropyladenosine) stimulates IL-6 expression in the human astrocytoma cell line U373 MG via the A 2b receptor. The mechanism by which NECA promotes astrocytic IL-6 expression has not been identified. By using various inhibitors of signal transduction, we found that p38 mitogen-activated protein kinases (MAPK) activation (inhibitor SB202190), but not extracellular signal-regulated kinase (ERK) (PD98059) and c-jun N-terminal kinase (JNK)(SP600125), is essential in the NECA-induced signalling cascade that leads to the increase in IL-6 synthesis in U373 MG cells. Results obtained with protein kinase C (PKC) inhibitors that have different substrate specificities, indicated that the PKC delta and epsilon isoforms are also involved in adenosine receptor A 2b dependent upregulation of IL-6 expression. This is supported by the fact that NECA induced the activation of PKC delta and epsilon in U373 MG cells.