Analysis of the mechanism for the development of allergic skin inflammation and the application for its treatment: aspirin modulation of IgE-dependent mast cell activation: role of aspirin-induced exacerbation of immediate allergy.
Aspirin (acetylsalicylic acid) is a well-known nonsteroidal anti-inflammatory drug that can potentiate some acute allergies and causes adverse immunological reactions collectively referred to as aspirin intolerance, a disorder that induces urticaria, asthma, and anaphylaxis in response to oral administration of the drug. Aspirin also potentiates some acute allergies such as food-dependent exercise-induced anaphylaxis (FDEIA), a food allergy induced by physical exercise. The anti-inflammatory actions as well as the adverse immunological effects have been thought to be primarily due to inhibition of cyclooxygenase activity. However, a growing body of evidence suggests that mechanisms unrelated to inhibition of prostaglandin synthesis are involved. One key feature of aspirin intolerance is the overproductions of cysteinyl leukotrienes (LTs), in which mast cells have been implicated to play a role. In this review, we provide an overview of our current knowledge about the regulatory mechanisms of LTC(4) secretion in mast cells and its modulation by aspirin, with a special emphasis on the role of Ca(2+) signals. We also introduced our recent findings that mast cells express dihydropyridine-sensitive L-type Ca(2+) channels (LTCCs) and that Ca(2+) channels of this kind mediate aspirin modulation of LTC(4) secretion in mast cells.
Suzuki
Yoshihiro
Y
Division of Molecular Cell Immunology and Allergology, Nihon University Graduate School of Medical Science, Japan. ysuzuki@med.nihon-u.ac.jp
Ra
Chisei
C
D001241:Aspirin / Q000009:adverse effects* / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000209:etiology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D018836:Inflammation Mediators / Q000494:pharmacology; D017997:Leukotriene C4 / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D018448:Models, Immunological
D020746:Calcium Channels, L-Type; D018836:Inflammation Mediators; D017997:Leukotriene C4; D007073:Immunoglobulin E; D001241:Aspirin