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Inhibitors of PI 3‐kinase and MEK kinase differentially affect mediator secretion from immunologically activated human basophils
Author(s) -
Gibbs Bernhard F.,
Grabbe Jurgen
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.65.6.883
Subject(s) - biology , secretion , mediator , kinase , affect (linguistics) , microbiology and biotechnology , protein kinase a , pi , immunology , biochemistry , psychology , communication
Effects of inhibitors of PI 3‐kinase and MEK kinases were investigated on histamine, leukotriene C 4 (LTC 4 ), and cytokine release from human basophils stimulated with anti‐IgE. The PI 3‐kinase antagonists wortmannin (> 10 nM) and LY 294002 (> 1 μM) strongly inhibited anti‐IgE‐induced release of all mediators by 40–100%. This was contrasted by the effects of the MEK kinase inhibitor PD 098059, which weakly inhibited histamine, interleukin (IL)‐4, and IL‐13 release but was substantially more efficacious at blocking LTC4 production (> 70% at 10 μM). Previous studies have shown that arachidonic acid synthesis is controlled by MEK kinases. We observed that wortmannin, LY 294002, and PD 098059 reduce basophil ERK‐1,2 activation, thus implying that, with regard to arachidonic acid metabolism, MEK kinases are a downstream target for PI‐3‐kinase. Our results demonstrate a universal regulatory role played by PI 3‐kinases in basophil mediator production and release, whereas MEK kinase signaling is largely limited to controlling arachidonic acid metabolism. J. Leukoc. Biol. 65: 883–890; 1999.