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:info:doi/10.1084/jem.20021824

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論文情報

タイトル	Increased Susceptibility to LPS-induced Endotoxin Shock in Secretory Leukoprotease Inhibitor (SLPI)-deficient Mice
著者	Nakamura, Akira Nakamura, Akira
	Mori, Yuriko Mori, Yuriko
	Hagiwara, koichi Hagiwara, koichi
	Suzuki, Takuji Suzuki, Takuji
	Sakakibara, Tomohiro Sakakibara, Tomohiro
	Kikuchi, Toshiaki Kikuchi, Toshiaki
	Igarashi, Takayuki Igarashi, Takayuki
	Ebina, Masahiro Ebina, Masahiro
	Abe, Tatsuya Abe, Tatsuya
	Miyazaki, Junichi Miyazaki, Junichi
	Takai, Toshiyuki Takai, Toshiyuki
	Nukiwa, Toshihiro 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.
公開者	The Rockefeller University Press
掲載誌名	Journal of Experimental Medicine
巻	197
号	5
開始ページ	669
終了ページ	674
刊行年月	2003-03-03
ISSN	00221007
NCID	AA00697559
DOI (出版社版)	info:doi/10.1084/jem.20021824
URL	http://hdl.handle.net/11094/23109
権利情報	© 2003 Rockefeller University Press
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII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.197(5) P.669-P.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
DCTERMS.issued" scheme="DCTERMS.W3CDTF	2003-03-03
DC.identifier	info:doi/10.1084/jem.20021824
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/23109
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
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_issn	00221007
citation_doi	info:doi/10.1084/jem.20021824
citation_public_url	http://hdl.handle.net/11094/23109
citation_keywords	endotoxin shock
	innate immunity
	LPS
	NF-κB
	SLPI

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