TREM-1--expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases

Schenk, Mirjam; Bouchon, Axel; Seibold, Frank; Mueller, Christoph (2007). TREM-1--expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases. Journal of clinical investigation, 117(10), pp. 3097-3106. Ann Arbor, Mich.: American Society for Clinical Investigation 10.1172/JCI30602

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Triggering receptor expressed on myeloid cells-1 (TREM-1) potently amplifies acute inflammatory responses by enhancing degranulation and secretion of proinflammatory mediators. Here we demonstrate that TREM-1 is also crucially involved in chronic inflammatory bowel diseases (IBD). Myeloid cells of the normal intestine generally lack TREM-1 expression. In experimental mouse models of colitis and in patients with IBD, however, TREM-1 expression in the intestine was upregulated and correlated with disease activity. TREM-1 significantly enhanced the secretion of relevant proinflammatory mediators in intestinal macrophages from IBD patients. Blocking TREM-1 by the administration of an antagonistic peptide substantially attenuated clinical course and histopathological alterations in experimental mouse models of colitis. This effect was also seen when the antagonistic peptide was administered only after the first appearance of clinical signs of colitis. Hence, TREM-1-mediated amplification of inflammation contributes not only to the exacerbation of acute inflammatory disorders but also to the perpetuation of chronic inflammatory disorders. Furthermore, interfering with TREM-1 engagement leads to the simultaneous reduction of production and secretion of a variety of pro-inflammatory mediators such as TNF, IL-6, IL-8 (CXCL8), MCP-1 (CCL2), and IL-1beta. Therefore, TREM-1 may also represent an attractive target for the treatment of chronic inflammatory disorders.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Schenk, Mirjam; Seibold, Frank Werner and Müller, Christoph

ISSN:

0021-9738

ISBN:

17853946

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

Christa Hagert

Date Deposited:

04 Oct 2013 14:54

Last Modified:

27 Jul 2017 12:58

Publisher DOI:

10.1172/JCI30602

PubMed ID:

17853946

Web of Science ID:

000249894400040

BORIS DOI:

10.7892/boris.22828

URI:

https://boris.unibe.ch/id/eprint/22828 (FactScience: 37210)

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