IL-6 expression induced by adenosine A sub(2b) receptor stimulation in U373 MG cells depends on p38 mitogen activated kinase and protein kinase C
Adenosine binds to a class of G-protein coupled receptors, which are further distinguished as A sub(1), A sub(2a), A sub(2b) and A sub(3) adenosine receptors. As we have shown earlier, the stable adenosine analogue NECA (N6-(R)- phenylisopropyladenosine) stimulates IL-6 expression in the human astro...
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Veröffentlicht in: | Neurochemistry international 2005-05, Vol.46 (6), p.501-512 |
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Sprache: | eng |
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Zusammenfassung: | Adenosine binds to a class of G-protein coupled receptors, which are further distinguished as A sub(1), A sub(2a), A sub(2b) and A sub(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 sub(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 sub(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. |
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ISSN: | 0197-0186 |
DOI: | 10.1016/j.neuint.2004.11.009 |