Abstract |
The intestinal microbiota has been linked to inflammatory bowel diseases (IBD), and oral treatment with specific bacteria can ameliorate IBD. One bacterial mixture, VSL#3, containing Lactobacillus, Bifidobacterium, and Streptococcus, was clinically shown to reduce inflammation in IBD patients and normalize intestinal levels of IP-10, a lymphocyte-recruiting chemokine, in a murine colitis model. We identified Lactobacillus paracasei prtP-encoded lactocepin as a protease that selectively degrades secreted, cell-associated, and tissue-distributed IP-10, resulting in significantly reduced lymphocyte recruitment after intraperitoneal injection in an ileitis model. A human Lactobacillus casei isolate was also found to encode lactocepin and degrade IP-10. L. casei feeding studies in a murine colitis model (T cell transferred Rag2(-/-) mice) revealed that a prtP-disruption mutant was significantly less potent in reducing IP-10 levels, T cell infiltration and inflammation in cecal tissue compared to the isogenic wild-type strain. Thus, lactocepin-based therapies may be effective treatments for chemokine-mediated diseases like IBD.
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Authors | Marie-Anne von Schillde, Gabriele Hörmannsperger, Monika Weiher, Carl-Alfred Alpert, Hannes Hahne, Christine Bäuerl, Karolien van Huynegem, Lothar Steidler, Tomas Hrncir, Gaspar Pérez-Martínez, Bernhard Kuster, Dirk Haller |
Journal | Cell host & microbe
(Cell Host Microbe)
Vol. 11
Issue 4
Pg. 387-96
(Apr 19 2012)
ISSN: 1934-6069 [Electronic] United States |
PMID | 22520466
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- Chemokine CXCL10
- Serine Endopeptidases
- lactocepin
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Topics |
- Amino Acid Sequence
- Animals
- Chemokine CXCL10
(genetics, immunology, metabolism)
- Colitis
(immunology, metabolism, microbiology, therapy)
- Disease Models, Animal
- Female
- Humans
- Lactobacillus
(enzymology, immunology)
- Lacticaseibacillus casei
(enzymology, immunology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Molecular Sequence Data
- Probiotics
(therapeutic use)
- Protein Transport
- Proteolysis
- Serine Endopeptidases
(immunology, metabolism)
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