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ID 115394
Title Alternative
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
Author
Kondo, Mayo Tokushima University
Bando, Hiroki Tokushima University
Keywords
Lysophosphatidic acid
LPA2 antagonist
allergic airway inflammation
Th2 cells
Content Type
Thesis or Dissertation
Description
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.
Journal Title
International Archives of Allergy and Immunology
ISSN
10182438
14230097
NCID
AA10838704
AA12783716
Publisher
karger
Volume
182
Issue
1
Start Page
1
End Page
13
Published Date
2020-08-26
Remark
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。
Rights
© 2020 S. Karger AG, Basel
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3463号
Diploma Number
甲医第1469号
Granted Date
2020-10-22
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital