Expression and Regulation of the Chemokine CXCL16 in Crohn's Disease and Models of Intestinal Inflammation

被引:40
作者
Diegelmann, Julia
Seiderer, Julia
Niess, Jan-Hendrik [1 ]
Haller, Dirk [2 ]
Goeke, Burkhard
Reinecker, Hans-Christian [3 ,4 ,5 ]
Brand, Stephan
机构
[1] Univ Ulm, Dept Internal Med 1, D-7900 Ulm, Germany
[2] Tech Univ Munich, ZIEL Res Ctr Nutr & Food Sci, Munich, Germany
[3] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA
[4] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA
[5] Harvard Univ, Sch Med, Boston, MA USA
关键词
Crohn's disease; ulcerative colitis; inflammatory bowel disease; chemokine; CXCL16; CXCR6; mouse model; intestinal inflammation; intestinal epithelial cells; cytokine; signaling; EPITHELIAL-CELLS; RECEPTOR CXCR6; PROTEIN-KINASE; CANCER CELLS; TNF-ALPHA; LIGAND; FRACTALKINE; ACTIVATION; MIGRATION; PROLIFERATION;
D O I
10.1002/ibd.21306
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 TNF Delta ARE 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 TNF Delta ARE 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.
引用
收藏
页码:1871 / 1881
页数:11
相关论文
共 45 条
[41]   p38 mitogen-activated protein kinase is activated and linked to TNF-α signaling in inflammatory bowel disease [J].
Waetzig, GH ;
Seegert, D ;
Rosenstiel, P ;
Nikolaus, S ;
Schreiber, S .
JOURNAL OF IMMUNOLOGY, 2002, 168 (10) :5342-5351
[42]  
Wågsäter D, 2004, ANTICANCER RES, V24, P3711
[43]   RETRACTED: CXCR6 Induces Prostate Cancer Progression by the AKT/Mammalian Target of Rapamycin Signaling Pathway (Retracted Article) [J].
Wang, Jianhua ;
Lu, Yi ;
Wang, Jingchen ;
Koch, Alisa E. ;
Zhang, Jian ;
Taichman, Russell S. .
CANCER RESEARCH, 2008, 68 (24) :10367-10376
[44]   T cells, dendritic cells and epithelial cells in intestinal homeostasis [J].
Westendorf, Astrid M. ;
Fleissner, Diana ;
Hansen, Wiebke ;
Buer, Jan .
INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, 2010, 300 (01) :11-18
[45]   Expression cloning of the STRL33/BONZO/TYMSTR ligand reveals elements of CC, CXC, and CX3C chemokines [J].
Wilbanks, A ;
Zondlo, SC ;
Murphy, K ;
Mak, S ;
Soler, D ;
Langdon, P ;
Andrew, DP ;
Wu, LJ ;
Briskin, M .
JOURNAL OF IMMUNOLOGY, 2001, 166 (08) :5145-5154