Blank Cover Image

Sphingosine-1-phosphate receptor 2 protects against anaphylactic shock through suppression of endothelial nitric oxide synthase in mice

フォーマット:
論文
責任表示:
Cui, Hong ; Okamoto, Yasuo ; Yoshioka, Kazuaki ; Du, Wa ; Takuwa, Noriko ; Zhang, Wei ; Asano, Masahide ; Shibamoto, Toshishige ; Takuwa, Yoh
言語:
英語
出版情報:
Elsevier, 2013-11-01
著者名:
Cui, Hong
Okamoto, Yasuo
Yoshioka, Kazuaki
Du, Wa
Takuwa, Noriko
Zhang, Wei
Asano, Masahide
Shibamoto, Toshishige
Takuwa, Yoh
続きを見る
掲載情報:
Journal of Allergy and Clinical Immunology
ISSN:
0091-6749  CiNii Articles  Webcat Plus  JAIRO
巻:
132
通号:
5
開始ページ:
1205
終了ページ:
1214
バージョン:
author
概要:
Background Sphingosine-1-phosphate receptor 2 (S1P2) is expressed in vascular endothelial cells (ECs). However, the role of S1P 2 in vascular barrier integrity and anaphylaxis is not well understood. Endothelial nitric oxide synthase (eNOS) generates nitric oxide to mediate vascular leakage, compromising survival in patients with anaphylaxis. We recently observed that endothelial S1P2 inhibits Akt, an activating kinase of eNOS. Objective We tested the hypothesis that endothelial S1P 2 might suppress eNOS, exerting a protective effect against endothelial barrier disruption and anaphylaxis. Methods Mice deficient in S1P2 and eNOS underwent antigen challenge or platelet-activating factor (PAF) injection. Analyses were performed to examine vascular permeability and the underlying mechanisms. Results S1pr2 deletion augmented vascular leakage and lethality after either antigen challenge or PAF injection. PAF injection induced activation of Akt and eNOS in the aortas and lungs of S1pr2-null mice, which were augmented compared with values seen in wild-type mice. Consistently, PAF-induced increase in cyclic guanosine monophosphate levels in the aorta was enhanced in S1pr-null mice. Genetic Nos3 deletion or pharmacologic eNOS blockade protected S1pr2-null mice from aggravation of barrier disruption after antigen challenge and PAF injection. ECs isolated from S1pr2-null mice exhibited greater stimulation of Akt and eNOS, with enhanced nitric oxide production in response to sphingosine-1-phosphate or PAF, compared with that seen in wild-type ECs. Moreover, S1pr2-deficient ECs showed more severe disassembly of adherens junctions with augmented S-nitrosylation of β-catenin in response to PAF, which was restored by pharmacologic eNOS blockade. Conclusion S1P2 diminishes harmful robust eNOS stimulation and thereby attenuates vascular barrier disruption, suggesting potential usefulness of S1P2 agonists as novel therapeutic agents for anaphylaxis. © 2013 American Academy of Allergy, Asthma & Immunology. 続きを見る
URL:
http://hdl.handle.net/2297/36259

類似資料:

1
 
2
 
3
 
4
 
5
 
6
 
7
 
8
 
9
 
10
 
11
 
12
 

Cui, Hong, Okamoto, Yasuo, Yoshioka, Kazuaki, Du, Wa, Takuwa, Noriko, Zhang, Wei, Asano, Masahide, Shibamoto, …

Elsevier

Takuwaa, Yoh, Okamoto, Yasuo, Yoshioka, Kazuaki, Takuwa, Noriko

International Union of Biochemistry and Molecular Biology, Inc. / Wiley-Blackwell

Juanjuan, Zhao, Okamoto, Yasuo, Takuwa, Yoh

金沢大学十全医学会 = The Juzen Medical Society Kanazawa University

Du, Wa, Takuwa, Noriko, Yoshioka, Kazuaki, Okamoto, Yasuo, Gonda, Koichi, Sugihara, Kazushi, Fukamizu, Akiyoshi, Asano, …

American Association for Cancer Research

Takuwa, Yoh, Okamoto, Yasuo, Yoshioka, Kazuaki, Takuwa, Noriko

International Union of Biochemistry and Molecular Biology, Inc / Wiley-Blackwell

Zhao, Juanjuan, Okamoto, Yasuo, Asano, Yuya, Ishimaru, Kazuhiro, Aki, Sho, Yoshioka, Kazuaki, Takuwa, Noriko, Wada, …

Public Library of Science

Takuwa, Yoh, Okamoto, Yasuo, Yoshioka, Kazuaki, Takuwa, Noriko

Elsevier

Wang, Fei, Okamoto, Yasuo, Inoki, Isao, Yoshioka, Kazuaki, Du, Wa, Qi, Xun, Takuwa, Noriko, Gonda, Koichi, Yamamoto, …

American Society for Clinical Investigation

Takuwa, Yoh, Ikeda, Hitoshi, Okamoto, Yasuo, Takuwa, Noriko, Yoshioka, Kazuaki

Elsevier

Aki, Sho, Yoshioka, Kazuaki, Okamoto, Yasuo, Takuwa, Noriko, Takuwa, Yoh

American Society for Biochemistry and Molecular Biology

Takuwa, Yoh, Okamoto, Yasuo, Yoshioka, Kazuaki, Takuwa, Noriko

Elsevier

Yoshioka, Kazuaki, Yoshida, Kotaro, Cui, Hong, Wakayama, Tomohiko, Takuwa, Noriko, Okamoto, Yasuo, Du, Wa, Qi, Xun, …

Nature Publishing Group