Increased susceptibility to LPS-induced endotoxin shock in secretory leukoprotease inhibitor (SLPI)-deficient mice

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

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

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-/- macrophages 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.

Original languageEnglish
Pages (from-to)669-674
Number of pages6
JournalJournal of Experimental Medicine
Volume197
Issue number5
DOIs
Publication statusPublished - 2003 Mar 3

Keywords

  • Endotoxin shock
  • Innate immunity
  • LPS
  • NF-κB
  • SLPI

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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