1. Syk 阻害薬 Entospletinib のアレルギー抑制効果.
- Author
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八巻 耕也 and 犬小 山豊
- Subjects
MAST cells ,ORAL drug administration ,ANTIALLERGIC agents ,ALLERGIES ,ACUTE diseases ,CELL culture ,IMMUNOGLOBULIN E ,WNT signal transduction - Abstract
Allergy is a life-threatening, acute disease mainly caused by mediators released from immunoglobulin E and allergen-activated mast cells. Syk, an intracellular signaling molecule important for cancer development, was supposed to have a critical role in mast cell activation. Thus, we clarified the anti-allergic effect of potent Syk inhibitor entospletinib in vivo mouse allergic model and in vitro cell cultures. Immunoglobulin E and allergen-mediated degranulation of rat basophilic leukemia RBL2H3 cells was suppressed by quite low concentrations of entospletinib (10 nM or more) occurring in 20 min without affecting cell viability. The drug treatment (3 nM or more) also inhibited cytokine secretion from the immunoglobulin E and allergen-activated RBL2H3 cells within 4 h. Rectal temperature decrease caused by passive systemic anaphylaxis in mice was diminished obviously by oral administration of a small amount of entospletinib (0.3 mg/mouse). Increase of the concentration of mouse mast cell protease-1, an indicator of mast cell activation, in serum of mice upon the passive systemic anaphylaxis induction was also attenuated by the oral administration of entospletinib, similar to its inhibitory effect on RBL2H3 activation observed in vitro. These findings indicated that Syk inhibitor entospletinib inhibited allergic reaction via blunting mast cell activation. Syk inhibitor entospletinib and its derivatives might be good candidates as anti-allergic drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2023