2012 Fiscal Year Final Research Report
analysis of the mechanism for aspirin modulation of IgE-dependent mast cell activation
| Project/Area Number |
22591232
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Yoshihiro 日本大学, 医学部, 助教 (80206549)
RA Chisei 日本大学, 医学部, 教授 (60230851)
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| Project Period (FY) |
2010 – 2012
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| Keywords | アスピリン / マスト細胞 / L 型カルシウムチャンネル / α1c (Cav1.2) |
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| Research Abstract |
Aspirin induces immunological side effects, which are collectively referred to as aspirin intolerance. Aspirin intolerance is a disorder that induces urticaria, asthma and anaphylaxis in response to oral administration of the drug. One key clinical feature of aspirin intolerance is overproduction of LTC4, LTD4 and LTE4 in mast cells, which are all sequentially synthesized from arachidonate. These cysteinyl LTs (cys-LTs) are potent proinflammatory mediators and cause smooth muscle contraction and increased vascular permeability. Recently, we showed that aspirin and salicylates upregulate IgE-mediated Ca2+ responses and LTC4 secretion in mast cells (Togo et al., 2009; Suzuki et al., 2010; Suzuki et al., 2010). Strikingly, however both drugs inhibited rather than facilitated the activation of store-operated Ca2+ channels, the major pathway for Ca2+ influx and LTC4 secretion. Instead, they facilitated the activation of a non-SOCC. In the present study, we attempted to identify the molecular entity of the aspirin-sensitive Ca2+ channels and clarify the molecular mechanisms underlying their activation by aspirin. Our data show that aspirin and salicylates facilitate secretion responses through Cav1.2 L-type Ca2+ channel (LTCC) activation and suggest that both drugs exert the effects via mitochondrial reactive oxygen species (ROS) production and depolarization.
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Research Products
(4 results)
