Fiebich Bernd L, Akundi Ravi S, Biber Knut, Hamke Maike, Schmidt Claudia, Butcher Russ D, van Calker Dietrich, Willmroth Frank
University of Freiburg Medical School, Department of Psychiatry and Psychotherapy, Neurochemistry Research Group, Hauptstrasse 5, D-79104 Freiburg, Germany.
Neurochem Int. 2005 May;46(6):501-12. doi: 10.1016/j.neuint.2004.11.009.
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.
腺苷与一类G蛋白偶联受体结合，这些受体又进一步分为A(1)、A(2a)、A(2b)和A(3)腺苷受体。正如我们之前所表明的，稳定的腺苷类似物NECA（N6-(R)-苯异丙基腺苷）通过A(2b)受体刺激人星形细胞瘤细胞系U373 MG中白细胞介素-6（IL-6）的表达。NECA促进星形细胞IL-6表达的机制尚未明确。通过使用各种信号转导抑制剂，我们发现p38丝裂原活化蛋白激酶（MAPK）的激活（抑制剂SB202190），而非细胞外信号调节激酶（ERK）（PD98059）和c-jun氨基末端激酶（JNK）（SP600125），在NECA诱导的信号级联反应中至关重要，该信号级联反应导致U373 MG细胞中IL-6合成增加。用具有不同底物特异性的蛋白激酶C（PKC）抑制剂获得的结果表明，PKCδ和ε亚型也参与腺苷受体A(2b)依赖性的IL-6表达上调。这一观点得到了以下事实的支持：NECA在U373 MG细胞中诱导了PKCδ和ε的激活。
