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- W3011899200 abstract "The functional inhibition of mast cells, which serve as a key effector cells in allergic reactions may be a specific target for treating immunoglobulin (Ig)E-mediated allergic reactions, which occur in various allergic diseases including anaphylaxis, asthma, and atopic dermatitis. In this study, we demonstrated the effects of dabrafenib, a therapeutic agent used to treat metastatic melanoma, with a focus on mast cell activation and local cutaneous anaphylaxis. In two types of mast cells (RBL-2H3 and mouse bone marrow-derived mast cells), dabrafenib (0.01, 0.1, 1 μM) pretreatment significantly decreased IgE-induced degranulation, intracellular calcium influx, and the activity of intracellular signaling molecules, such as Lyn, Syk, Akt, and PLCγ. Dabrafenib ameliorated mRNA and protein expression levels of interleukin-4 and tumor necrosis factor-α by the reduction of nuclear localization of nuclear factor-κB and nuclear factor of activated T-cells. In passive cutaneous anaphylaxis, oral administration of dabrafenib (0.1, 1, 10 mg/kg) reduced local pigmentation and ear thickness in a dose-dependent manner. Taken together, these results suggest that dabrafenib is a therapeutic drug candidate that controls IgE-mediated allergic inflammatory diseases through suppression of mast cell activity." @default.
- W3011899200 created "2020-03-23" @default.
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- W3011899200 date "2020-06-01" @default.
- W3011899200 modified "2023-10-18" @default.
- W3011899200 title "The suppressive effect of dabrafenib, a therapeutic agent for metastatic melanoma, in IgE-mediated allergic inflammation" @default.
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- W3011899200 doi "https://doi.org/10.1016/j.intimp.2020.106398" @default.
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