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