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ID 115394
タイトル別表記
リゾホスファチジン酸はTh2細胞の分化を制御し、その拮抗薬はアレルギー性気道炎症を抑制する
Lysophosphatidic Acid Induces Allergic Inflammation
著者
近藤, 真代 徳島大学大学院医科学教育部(医学専攻)
Bando, Hiroki Tokushima University
キーワード
Lysophosphatidic acid
LPA2 antagonist
allergic airway inflammation
Th2 cells
資料タイプ
学位論文
抄録
Background: Lysophosphatidic acid (LPA), a prototypic member of a large family of lysophospholipids, has been recently shown to play a role in immune responses to respiratory diseases. The involvement of LPA in allergic airway inflammation has been reported, but the mechanism remains unclear. Object: We analyzed the biological activity of LPA in vitro and in vivo and investigated its role in allergic inflammation in mice using an LPA receptor 2 (LPA2) antagonist. Methods: We used a murine model with acute allergic inflammation, in which mice are sensitized and challenged with house dust mite, and analyzed airway hyperresponsiveness (AHR), pathological findings, Th2 cytokines, and IL-33 in bronchoalveolar lavage fluid (BALF) and lung homogenates. The effect of LPA on Th2 differentiation and cytokine production was examined in vitro using naive CD4+ T cells isolated from splenocytes. We also investigated in vivo the effects of LPA on intranasal administration in mice. Results: The LPA2 antagonist suppressed the increase of AHR, the number of total cells, and eosinophils in BALF and lung tissue. It also decreased the production of IL-13 in BALF and IL-33 and CCL2 in the lung. LPA promoted Th2 cell differentiation and IL-13 production by Th2 cells in vitro. Nasal administration of LPA significantly increased the number of total cells and IL-13 in BALF via regulating the production of IL-33 and CCL-2-derived infiltrating macrophages. Conclusion: These findings suggest that LPA plays an important role in allergic airway inflammation and that the blockade of LPA2 might have therapeutic potential for bronchial asthma.
掲載誌名
International Archives of Allergy and Immunology
ISSN
10182438
14230097
cat書誌ID
AA10838704
AA12783716
出版者
karger
182
1
開始ページ
1
終了ページ
13
発行日
2020-08-26
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Mayo Kondoの学位論文として提出され,学位審査・授与の対象となっている。
権利情報
© 2020 S. Karger AG, Basel
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3463号
学位記番号
甲医第1469号
学位授与年月日
2020-10-22
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院