Expression and regulation of the chemokine CXCL16 in Crohn's disease and models of intestinal inflammation (original) (raw)

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Julia Diegelmann, PhD ,

1Department of Internal Medicine II—Grosshadern, University of Munich, Munich, Germany;

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Julia Seiderer, MD ,

1Department of Internal Medicine II—Grosshadern, University of Munich, Munich, Germany;

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Jan-Hendrik Niess, MD ,

2Department of Internal Medicine I, University of Ulm, Ulm, Germany;

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Dirk Haller, PhD ,

3ZIEL - Research Centre for Nutrition and Food Science, Biofunctionality, Technische Universität, München, Germany;

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Burkhard Göke, MD ,

1Department of Internal Medicine II—Grosshadern, University of Munich, Munich, Germany;

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Hans-Christian Reinecker, MD ,

Hans-Christian Reinecker, MD

4Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

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Stephan Brand, MD

1Department of Internal Medicine II—Grosshadern, University of Munich, Munich, Germany;

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Received:

01 February 2010

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Julia Diegelmann, Julia Seiderer, Jan-Hendrik Niess, Dirk Haller, Burkhard Göke, Hans-Christian Reinecker, Stephan Brand, Expression and regulation of the chemokine CXCL16 in Crohn's disease and models of intestinal inflammation, Inflammatory Bowel Diseases, Volume 16, Issue 11, 1 November 2010, Pages 1871–1881, https://doi.org/10.1002/ibd.21306
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Background

CXCL16 mediates adhesion and phagocytosis of both Gram-negative and Gram-positive bacteria and is a strong chemoattractant for CXCR6+ T cells. In this study, we determined the so far unknown expression and signal transduction of the novel CXCL16–CXCR6 chemokine–ligand receptor system in intestinal inflammation in vivo and in vitro.

Methods

CXCL16 mRNA was measured by quantitative PCR in human colonic biopsies of patients with Crohn's disease (CD) as well as in the TNFΔARE mouse model of ileitis and in murine cytomegalovirus (MCMV)–induced colitis. CXCL16 serum levels were analyzed by ELISA. CXCL16-induced signal transduction was analyzed in intestinal epithelial cells with phospho-specific antibodies for mitogen-activated protein (MAP) kinases and Akt.

Results

We found an inverse expression pattern of CXCL16 and CXCR6, with highest CXCL16 mRNA expression in the proximal murine small intestine and the highest CXCR6 mRNA expression in the distal colon. CXCL16 and CXCR6 mRNA were expressed in colorectal cancer (CRC)–derived intestinal epithelial cell (IEC) lines. CRC-expressed CXCR6 was functional, as demonstrated by CXCL16-induced MAP kinase and Akt activation. Intestinal CXCL16 expression was elevated in the TNFΔARE mouse model of ileitis and in MCMV-induced colitis (P < 0.05) and in the sera and colons of patients with CD (P < 0.05), where its expression correlated highly with CXCR6 and IL-8 levels (r = 0.85 and 0.89, respectively).

Conclusions

CRC-derived IECs express the functional CXCL16 receptor CXCR6. CXCL16 mRNA and protein expression is up-regulated in intestinal inflammation in vitro and in CD patients, suggesting an important role for this chemokine in intestinal inflammation. Inflamm Bowel Dis 2010

Crohn's disease, ulcerative colitis, inflammatory bowel disease, chemokine, CXCL16, CXCR6, mouse model, intestinal inflammation, intestinal epithelial cells, cytokine, signaling

© 2010 Crohn's & Colitis Foundation of America, Inc.

Topic:

• signal transduction
• inflammation
• chemokines
• crohn's disease
• inflammatory bowel disease
• intestines
• rna, messenger
• colon
• mice
• epithelial cells
• proto-oncogene proteins c-akt

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