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PMID: 12615907 Published · ppublish English Journal Article

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

The Journal of experimental medicine ·Vol. 197 ·No. 5 ·2003-03-03 ·Pages 669-74

Nakamura A, Mori Y, Hagiwara K, Suzuki T, Sakakibara T, Kikuchi T, Igarashi T, Ebina M, Abe T, Miyazaki J, Takai T, Nukiwa T

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 kappaB 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.

MeSH Terms
Animals B-Lymphocytes/drug effects,physiology Disease Susceptibility HMGB1 Protein/metabolism I-kappa B Proteins/metabolism Interleukin-1/metabolism Interleukin-6/metabolism Lipopolysaccharides/toxicity Macrophages/drug effects,physiology Mice Mice, Inbred C57BL Mice, Knockout NF-KappaB Inhibitor alpha NF-kappa B/metabolism Nitrates/metabolism Proteinase Inhibitory Proteins, Secretory Proteins/genetics,metabolism Secretory Leukocyte Peptidase Inhibitor Serine Proteinase Inhibitors/genetics,metabolism Shock, Septic/immunology,metabolism,mortality Survival Rate Tumor Necrosis Factor-alpha/metabolism
Chemicals
HMGB1 Protein I-kappa B Proteins Interleukin-1 Interleukin-6 Lipopolysaccharides NF-kappa B Nfkbia protein, mouse Nitrates Proteinase Inhibitory Proteins, Secretory Proteins Secretory Leukocyte Peptidase Inhibitor Serine Proteinase Inhibitors Slpi protein, mouse Tumor Necrosis Factor-alpha NF-KappaB Inhibitor alpha
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Nakamura Akira
Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
Mori Yuriko
Hagiwara Koichi
Suzuki Takuji
Sakakibara Tomohiro
Kikuchi Toshiaki
Igarashi Takayuki
Ebina Masahito
Abe Tatsuya
Miyazaki Junichi
Takai Toshiyuki
Nukiwa Toshihiro
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20021824
Published
2003-03-03
Pages
669-74
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193830
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20021824 PMC Full Text View journal details
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