Pharmacologic study of basophil histamine release induced by monocyte chemotactic protein-1 with kinase inhibitors.
Monocyte chemotactic protein-1 (MCP-1)/monocyte chemotactic activating factor has a potent histamine-releasing activity for basophils and is a major component of IgE-independent histamine-releasing factors (HRF). In this study, we examined the effect of a panel of kinase inhibitors on MCP-1-induced histamine release from human basophils to characterize the signaling pathway used by this chemokine. Genistein (3 micrograms/ml), an inhibitor of tyrosine kinase, inhibited MCP-1-induced histamine release by 44%. Wortmannin is a specific inhibitor of phosphatidylinositol 3 kinase (PI-3 kinase). It blocked MCP-1-induced histamine release with an IC50 of 3.3 x 10(-8) M indicating a role of PI-3 kinase in this reaction. KT5926, an inhibitor of myosin light chain kinase, also inhibited histamine release in response to MCP-1 with an IC50 of 10(-6) M. Staurosporine, a potent inhibitor of protein kinase C, although being not specific, augmented MCP-1-induced histamine release by 31.9% at 10(-6) M. These results indicate the possible involvement of a series of kinases, including PI-3 kinase, in the signal transduction pathway used by MCP-1.
Suzuki
M
M
Department of Respiratory Medicine, Kantou Central Hospital, Tokyo, Japan.
Hirai
K
K
Kitani
S
S
Takaishi
T
T
Kihara
H
H
Kasahara
T
T
Ito
K
K
Morita
Y
Y
D000470:Alkaloids / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism*; D014408:Biomarkers, Tumor; D002227:Carbazoles; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D019833:Genistein; D006636:Histamine Release; D006801:Humans; D007211:Indoles; D007529:Isoflavones / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015398:Signal Transduction; D019311:Staurosporine; D000090324:Tumor Protein, Translationally-Controlled 1; D000077191:Wortmannin
D000470:Alkaloids; D000730:Androstadienes; D014408:Biomarkers, Tumor; D002227:Carbazoles; D018932:Chemokine CCL2; D007211:Indoles; D007529:Isoflavones; D008222:Lymphokines; D000090324:Tumor Protein, Translationally-Controlled 1; C063769:KT 5926; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine; D000077191:Wortmannin