Differential role for mitogen-activated protein kinases in IgE-dependent signaling in human peripheral blood basophils: in contrast to p38 MAPK, c-Jun N-terminal kinase is poorly expressed and does not appear to control mediator release.
BACKGROUND
Exposure of human basophils to allergens results in a rapid secretion of histamine, LTC(4), IL-4 and IL-13, which dominate both the symptomology of allergic diseases and support the underlying Th2/IgE predominance associated with these reactions. The IgE-dependent release of these mediators in basophils crucially involves PI 3-kinase and the subsequent activation of p38 MAPK and ERK1&2. Here, we investigated the role of the third major member of the mitogen activated kinase family, namely the c-Jun amino terminal kinase (JNK), which is rapidly activated following IgE receptor cross-linking in murine mast cells.


METHODS
Human basophils were highly purified by magnetic cell sorting. The activities of various intracellular signaling components, in basophils that had been stimulated under various conditions, were assessed by Western blotting. Mediator secretions were also determined using either spectrofluorometric analysis (histamine) or ELISA (LTC(4), IL-4 and IL-13).


RESULTS
Our results show that while JNK is moderately expressed in human basophils, it is not consistently phosphorylated upon anti-IgE stimulation. Phosphorylation of the transcription factor c-Jun, a downstream target of JNK, was also undetected in contrast to p38 MAPK and ERK1&2, which were clearly activated following anti-IgE stimulation of the cells. Additionally, inhibitors of the JNK pathway failed to prevent basophil mediator release and had no effect on the phosphorylation of p38 MAPK or ERK1&2 at concentrations which were specific for JNK blockade.


CONCLUSIONS
These data suggest major differences in utilizing various members of the mitogen-activated kinase family in the signal transduction cascade of IgE-receptor-bearing cells.
Gibbs
Bernhard F
BF
Department of Dermatology, University of Lubeck, Lubeck, Germany. bfgibbs@gmx.de
Wolff
Helmut H
HH
Zillikens
Detlef
D
Grabbe
Jurgen
J
D001491:Basophils / Q000201:enzymology* / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007073:Immunoglobulin E; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases