Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-deficient Mice

Nakamura, Akira; Mori, Yuriko; Hagiwara, Koichi; Suzuki, Takuji; Sakakibara, Tomohiro; Kikuchi, Toshiaki; Igarashi, Takayuki; Ebina, Masahiro; Abe, Tatsuya; Miyazaki, Junichi; Takai, Toshiyuki; Nukiwa, Toshihiro

doi:https://doi.org/10.1084/jem.20021824

Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-deficient Mice

Nakamura, Akira; Mori, Yuriko; Hagiwara, Koichi et al.

Journal of Experimental Medicine, 2003, 197(5), 669-674

アクセス数:1,622件（2025-07-11 23:57 集計）

固定URL: https://hdl.handle.net/11094/23109

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タイトル	Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-deficient Mice
著者	NRID 1000040343090 1000040343090 著者名 Nakamura, Akira
	著者名 Mori, Yuriko
	NRID 1000020804371 1000020804371 著者名 Hagiwara, Koichi
	NRID 1000080344670 1000080344670 著者名 Suzuki, Takuji
	NRID 1000080422111 1000080422111 著者名 Sakakibara, Tomohiro
	NRID 1000020509418 1000020509418 著者名 Kikuchi, Toshiaki
	著者名 Igarashi, Takayuki
	著者名 Ebina, Masahiro
	NRID 1000070222651 1000070222651 著者名 Abe, Tatsuya
	NRID 1000080229830 1000080229830 著者名 Miyazaki, Junichi
	NRID 1000020187917 1000020187917 著者名 Takai, Toshiyuki
	NRID 1000040129036 1000040129036 著者名 Nukiwa, Toshihiro
キーワード等	endotoxin shock
	innate immunity
	LPS
	NF-κB
	SLPI
抄録	Secretory leukoprotease inhibitor (SLPI) protects tissue against the destructive action of neutrophil elastase at the site of inflammation. Recent studies on new functions of SLPI have demonstrated that SLPI may play a larger role in innate immunity than merely as a protease inhibitor. To clarify the functions of SLPI in bacterial infections, we generated SLPI-deficient mice (SLPI−/− mice) and analyzed their response to experimental endotoxin shock induced by lipopolysaccharide (LPS). SLPI−/− mice showed a higher mortality from endotoxin shock than did wild type mice. This may be explained in part by our observation that SLPI−/− macro-phages show higher interleukin 6 and high-mobility group (HMG)-1 production and nuclear factor κB activities after LPS treatment than do SLPI+/+ macrophages. SLPI also affects B cell function. SLPI−/− B cells show more proliferation and IgM production after LPS treatment than SLPI+/+ B cells. Our results suggest that SLPI attenuates excessive inflammatory responses and thus assures balanced functioning of innate immunity.
出版者	The Rockefeller University Press
収録物名	Journal of Experimental Medicine
巻(号)	197(5)
ページ	669-674
刊行年月	2003-03-03
言語	英語
ハンドルURL	https://hdl.handle.net/11094/23109
PISSN	00221007
NCID	AA00697559
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1084/jem.20021824
アクセス権	open access
権利情報	© 2003 Rockefeller University Press
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Experimental Medicine. 2003, 197(5), p. 669-674
DC.title	Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-deficient Mice
DC.creator	Nakamura, Akira
	Mori, Yuriko
	Hagiwara, Koichi
	Suzuki, Takuji
	Sakakibara, Tomohiro
	Kikuchi, Toshiaki
	Igarashi, Takayuki
	Ebina, Masahiro
	Abe, Tatsuya
	Miyazaki, Junichi
	Takai, Toshiyuki
	Nukiwa, Toshihiro
DC.publisher	The Rockefeller University Press
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2003-03-03
DC.identifier	https://doi.org/10.1084/jem.20021824
DC.subject	endotoxin shock
	innate immunity
	LPS
	NF-κB
	SLPI
DCTERMS.abstract	Secretory leukoprotease inhibitor (SLPI) protects tissue against the destructive action of neutrophil elastase at the site of inflammation. Recent studies on new functions of SLPI have demonstrated that SLPI may play a larger role in innate immunity than merely as a protease inhibitor. To clarify the functions of SLPI in bacterial infections, we generated SLPI-deficient mice (SLPI−/− mice) and analyzed their response to experimental endotoxin shock induced by lipopolysaccharide (LPS). SLPI−/− mice showed a higher mortality from endotoxin shock than did wild type mice. This may be explained in part by our observation that SLPI−/− macro-phages show higher interleukin 6 and high-mobility group (HMG)-1 production and nuclear factor κB activities after LPS treatment than do SLPI+/+ macrophages. SLPI also affects B cell function. SLPI−/− B cells show more proliferation and IgM production after LPS treatment than SLPI+/+ B cells. Our results suggest that SLPI attenuates excessive inflammatory responses and thus assures balanced functioning of innate immunity.
DC.rights	© 2003 Rockefeller University Press
DC.format	23109
citation_title	Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-deficient Mice
citation_author	Nakamura, Akira
	Mori, Yuriko
	Hagiwara, Koichi
	Suzuki, Takuji
	Sakakibara, Tomohiro
	Kikuchi, Toshiaki
	Igarashi, Takayuki
	Ebina, Masahiro
	Abe, Tatsuya
	Miyazaki, Junichi
	Takai, Toshiyuki
	Nukiwa, Toshihiro
citation_publisher	The Rockefeller University Press
citation_language	英語
citation_date	2003-03-03
citation_journal_title	Journal of Experimental Medicine
citation_volume	197
citation_issue	5
citation_firstpage	669
citation_lastpage	674
citation_doi	https://doi.org/10.1084/jem.20021824
citation_public_url	https://hdl.handle.net/11094/23109

Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-deficient Mice

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