Journal of Smooth Muscle Research
Online ISSN : 1884-8796
Print ISSN : 0916-8737
ISSN-L : 0916-8737
Original
Sustained exposure to prostaglandin D2 augments the contraction induced by acetylcholine via a DP1 receptor-mediated activation of p38 in bronchial smooth muscle of naive mice
Wataru SutoHiroyasu SakaiYoshihiko Chiba
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2019 Volume 55 Pages 1-13

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Abstract

Prostaglandin D2 (PGD2), one of the key lipid mediators of allergic airway inflammation, is increased in the airways of asthmatics. However, the role of PGD2 in the pathogenesis of asthma is not fully understood. In the present study, effects of PGD2 on smooth muscle contractility of the airways were determined to elucidate its role in the development of airway hyperresponsiveness (AHR). In a murine model of allergic asthma, antigen challenge to the sensitized animals caused a sustained increase in PGD2 levels in bronchoalveolar lavage (BAL) fluids, indicating that smooth muscle cells of the airways are continually exposed to PGD2 after the antigen exposure. In bronchial smooth muscles (BSMs) isolated from naive mice, a prolonged incubation with PGD2 (10−5 M, for 24 h) induced an augmentation of contraction induced by acetylcholine (ACh): the ACh concentration-response curve was significantly shifted upward by the 24-h incubation with PGD2. Application of PGD2 caused phosphorylation of ERK1/2 and p38 in cultured BSM cells: both of the PGD2-induced events were abolished by laropiprant (a DP1 receptor antagonist) but not by fevipiprant (a DP2 receptor antagonist). In addition, the BSM hyperresponsiveness to ACh induced by the 24-h incubation with PGD2 was significantly inhibited by co-incubation with SB203580 (a p38 inhibitor), whereas U0126 (a ERK1/2 inhibitor) had no effect on it. These findings suggest that prolonged exposure to PGD2 causes the BSM hyperresponsiveness via the DP1 receptor-mediated activation of p38. A sustained increase in PGD2 in the airways might be a cause of the AHR in allergic asthmatics.

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この記事はクリエイティブ・コモンズ [表示 - 非営利 4.0 国際]ライセンスの下に提供されています。
https://creativecommons.org/licenses/by-nc/4.0/deed.ja
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