IL-6 expression induced by adenosine A2b receptor stimulation in U373 MG cells depends on p38 mitogen activated kinase and protein kinase C

Bernd L Fiebich; Ravi S Akundi; Knut Biber; Maike Hamke; Claudia Schmidt; Russ D Butcher; Dietrich van Calker; Frank Willmroth

doi:10.1016/j.neuint.2004.11.009

IL-6 expression induced by adenosine A2b receptor stimulation in U373 MG cells depends on p38 mitogen activated kinase and protein kinase C

Neurochem Int. 2005 May;46(6):501-12. doi: 10.1016/j.neuint.2004.11.009.

Authors

Bernd L Fiebich¹, Ravi S Akundi, Knut Biber, Maike Hamke, Claudia Schmidt, Russ D Butcher, Dietrich van Calker, Frank Willmroth

Affiliation

¹ University of Freiburg Medical School, Department of Psychiatry and Psychotherapy, Neurochemistry Research Group, Hauptstrasse 5, D-79104 Freiburg, Germany. [email protected]

PMID: 15769552
DOI: 10.1016/j.neuint.2004.11.009

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine / metabolism*
Adenosine A2 Receptor Agonists
Astrocytoma / metabolism*
Cell Line, Tumor
Enzyme Inhibitors / pharmacology
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Extracellular Signal-Regulated MAP Kinases / genetics
Extracellular Signal-Regulated MAP Kinases / metabolism
Humans
Interleukin-6 / metabolism*
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
JNK Mitogen-Activated Protein Kinases / genetics
JNK Mitogen-Activated Protein Kinases / metabolism
Protein Kinase C / antagonists & inhibitors
Protein Kinase C / genetics
Protein Kinase C / metabolism*
Protein Kinase C-delta
Protein Kinase C-epsilon
RNA, Messenger / drug effects
RNA, Messenger / metabolism
Receptor, Adenosine A2B / metabolism*
Signal Transduction / drug effects
Signal Transduction / physiology*
Up-Regulation / drug effects
Up-Regulation / physiology
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases / genetics
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Adenosine A2 Receptor Agonists
Enzyme Inhibitors
Interleukin-6
RNA, Messenger
Receptor, Adenosine A2B
PRKCD protein, human
PRKCE protein, human
Protein Kinase C
Protein Kinase C-delta
Protein Kinase C-epsilon
Extracellular Signal-Regulated MAP Kinases
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
Adenosine