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- Title
Pharmacologic Study of Basophil Histamine Release Induced by Monocyte Chemotactic Protein-1 with Kinase Inhibitors.
- Authors
Suzuki, Masaru; Hirai, Koichi; Kitani, Seiichi; Takaishi, Toshiaki; Kihara, Hidetoshi; Kasahara, Tadashi; Ito, Koji; Morita, Yutaka
- Abstract
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 μg/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 × 10--8M 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--6M. Staurosporine, a potent inhibitor of protein kinase C, although being not specific, augmented MCP-1-induced histamine release by 31.9% at 10--6M. These results indicate the possible involvement of a series of kinases, including PI-3 kinase, in the signal transduction pathway used by MCP-1. Copyright © 1996 S. Karger AG, Basel
- Publication
International Archives of Allergy & Immunology, 1996, Vol 111, Issue 1, p18
- ISSN
1018-2438
- Publication type
Article
- DOI
10.1159/000237339