Shikonin inhibits IgE-mediated histamine release by human basophils and Syk kinase activity

• Published in: Inflammation research 2008-10, Vol.57 (10), p.484-488
• Main Authors: Takano-Ohmuro, H., Yoshida, L. S., Yuda, Y., Morioka, K., Kitani, S.
• Format: Article
• Language: English
• Subjects: Allergology; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Basophils - cytology; Basophils - drug effects; Basophils - immunology; Biomedical and Life Sciences; Biomedicine; Dermatology; Histamine Release - immunology; Humans; Immunoglobulin E - immunology; Immunology; Intracellular Signaling Peptides and Proteins - metabolism; Naphthoquinones - pharmacology; Neurology; Pharmacology/Toxicology; Protein-Tyrosine Kinases - metabolism; Rheumatology; Syk Kinase
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-008-8067-9

. Objective: Shikonin, a component of the herbal medicine “Shikon”, is known to suppress inflammatory reactions, but its molecular targets are not identified. This study examines the effect of shikonin on human basophil degranulation response and aims to identify its targets. Materials: Human basophils in isolated leukocytes from healthy volunteers’ peripheral blood; recombinant human Syk and Lyn tyrosine kinases. Methods: Histamine release from basophils stimulated with anti-IgE antibody was analyzed fluorimetrically. Syk and Lyn kinase activities were tested in Vitro with recombinant proteins and analyzed by off-chip mobility shift assay. Results: Shikonin dose-dependently inhibited the histamine release from basophils induced by anti-IgE antibody (IC 50 = 2.6 ± 1.0 µM; mean ± SEM). A search for the target(s) of shikonin in the signal cascade of IgE-mediated activation showed that it strongly inhibits Syk (IC 50 = 7.8 µM, in the recombinant kinase assay), which plays a pivotal role in the degranulation response. A less significant inhibition was found for Lyn, which phosphorylates FcεRI-βγ subunits and also Syk. Conclusions: These results indicate that the inhibition of Syk-dependent phosphorylation events might underlie the blocked histamine release from human basophils, thus contributing to the anti-inflammatory effects of shikonin.