Strong Overexpression of CXCR3 Axis Components in Childhood Inflammatory Bowel Disease

被引：52

作者：

Schroepf, Sebastian ^{[1
]}

Kappler, Roland ^{[1
]}

Brand, Stephan ^{[2
]}

Prell, Christine ^{[3
]}

Lohse, Peter ^{[4
]}

Glas, Juergen ^{[1
,5
]}

Hoster, Eva ^{[6
]}

Helmbrecht, Johanna ^{[1
]}

Ballauff, Antje ^{[7
]}

Berger, Michael ^{[1
]}

von Schweinitz, Dietrich ^{[1
]}

Koletzko, Sibylle ^{[3
]}

Lacher, Martin ^{[1
]}

机构：

[1] Univ Munich, Res Labs, Dept Pediat Surg, D-80337 Munich, Germany

[2] Univ Munich, Dept Med Grosshadern 2, Munich, Germany

[3] Univ Munich, Dept Pediat, Div Pediat Gastroenterol, Munich, Germany

[4] Univ Munich, Inst Clin Chem Grosshadern, Munich, Germany

[5] Rhein Westfal TH Aachen, Dept Human Genet, Aachen, Germany

[6] Univ Munich, Dept Med Informat Biometry & Epidemiol, Munich, Germany

[7] Univ Duisburg Essen, Univ Klinikum Essen, Div Pediat Gastroenterol, Essen, Germany

来源：

INFLAMMATORY BOWEL DISEASES | 2010年 / 16卷 / 11期

关键词：

Crohn's disease; Childhood onset; CXCR3; CXCL11; Inflammatory bowel disease; rs6817952; Ulcerative colitis; GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; CHEMOKINE RECEPTORS; EXPRESSION; CELLS; BLOCKADE; COLITIS; VARIANT; GENE;

D O I：

10.1002/ibd.21312

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background: Inflammatory bowel disease (IBD) is a polygenetic disorder. Our group previously showed that a variant within the CXCL9 gene is associated with pediatric Crohn's disease. As CXCL9, CXCL 10, and CXCL I I are the 3 ligands to the receptor CXCR3, the aim of this study was to investigate the colonic transcriptional activity of the CXCR3 axis and to perform SNP genotyping of a CXCL11 polymorphism in a large pediatric and adult IBD cohort. Methods: mRNA expression of CXCR3, CXCL9, CXCL10, CXCL11, and IL8 was analyzed in colonic biopsies using real-time PCR. CXCL11 rs6817952 nucleotide substitution was determined in 501 German individuals with IBD (336 CD, 165 UC) "including 258 children and 243 adults as well as in 231 controls by a TaqMan SNP genotyping assay. Results: CXCR3 axis genes were significantly overexpressed in inflamed colonic tissue of pediatric CD and UC patients. The prevalence of hetero- and homozygous variants of the rs6817952 genotype was higher in pediatric but not in adult CD patients compared with that in controls (P = 0.04). Moreover, carriers of the hetero- and homozygous genotype variants of rs6817952 were at increased risk for UC in all age groups (P = 0.009).

引用

页码：1882 / 1890

页数：9

共 33 条

[1] MECHANISMS OF DISEASE Inflammatory Bowel Disease [J].

Abraham, Clara ;

Cho, Judy H. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (21) :2066-2078

[2] Phenotypic and functional features of human Th17 cells [J].

Annunziato, Francesco ;

Cosmi, Lorenzo ;

Santarlasci, Veronica ;

Maggi, Laura ;

Liotta, Francesco ;

Mazzinghi, Benedetta ;

Parente, Eliana ;

Fili, Lucia ;

Ferri, Simona ;

Frosali, Francesca ;

Giudici, Francesco ;

Romagnani, Paola ;

Parronchi, Paola ;

Tonelli, Francesco ;

Maggi, Enrico ;

Romagnani, Sergio .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) :1849-1861

[3] Expression of chemokine receptors in normal and inflamed human intestine, tonsil, and liver - An immunohistochemical analysis with new monoclonal antibodies from the 8th international workshop and conference on human leucocyte differentiation antigens [J].

Autschbach, F ;

Funke, B ;

Katzenmeier, M ;

Gassler, N .

CELLULAR IMMUNOLOGY, 2005, 236 (1-2) :110-114

[4] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[5] Cell differentiation dependent expressed CCR6 mediates ERK-1/2, SAPK/JNK, and Akt signaling resulting in proliferation and migration of colorectal cancer cells [J].

Brand, S ;

Olszak, T ;

Beigel, F ;

Diebold, J ;

Otte, JM ;

Eichhorst, ST ;

Göke, B ;

Dambacher, J .

JOURNAL OF CELLULAR BIOCHEMISTRY, 2006, 97 (04) :709-723

[6] Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease [J].

Brand, S. .

GUT, 2009, 58 (08) :1152-1167

[7] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[8] A genome-wide association study identifies IL23R as an inflammatory bowel disease gene [J].

Duerr, Richard H. ;

Taylor, Kent D. ;

Brant, Steven R. ;

Rioux, John D. ;

Silverberg, Mark S. ;

Daly, Mark J. ;

Steinhart, A. Hillary ;

Abraham, Clara ;

Regueiro, Miguel ;

Griffiths, Anne ;

Dassopoulos, Themistocles ;

Bitton, Alain ;

Yang, Huiying ;

Targan, Stephan ;

Datta, Lisa Wu ;

Kistner, Emily O. ;

Schumm, L. Philip ;

Lee, Annette T. ;

Gregersen, Peter K. ;

Barmada, M. Michael ;

Rotter, Jerome I. ;

Nicolae, Dan L. ;

Cho, Judy H. .

SCIENCE, 2006, 314 (5804) :1461-1463

[9] The unique target specificity of a nonpeptide chemokine receptor antagonist: selective blockade of two Th1 chemokine receptors CCR5 and CXCR3 [J].

Gao, P ;

Zhou, XY ;

Yashiro-Ohtani, Y ;

Yang, YF ;

Sugimoto, N ;

Ono, S ;

Nakanishi, T ;

Obika, S ;

Imanishi, T ;

Egawa, T ;

Nagasawa, T ;

Fujiwara, H ;

Hamaoka, T .

JOURNAL OF LEUKOCYTE BIOLOGY, 2003, 73 (02) :273-280

[10] The ATG16L1 Gene Variants rs2241879 and rs2241880 (T300A) Are Strongly Associated With Susceptibility to Crohn's Disease in the German Population [J].

Glas, Jurgen ;

Konrad, Astrid ;

Schmechel, Silke ;

Dambacher, Julia ;

Seiderer, Julia ;

Schroff, Frieder ;

Wetzke, Martin ;

Roeske, Darina ;

Toeroek, Helga-Paula ;

Tonenchi, Laurian ;

Pfennig, Simone ;

Haller, Dirk ;

Griga, Thomas ;

Klein, Wolfram ;

Epplen, Joerg T. ;

Folwaczny, Christian ;

Lohse, Peter ;

Goeke, Burkhard ;

Ochsenkuehn, Thomas ;

Mussack, Thomas ;

Folwaczny, Matthias ;

Mueller-Myhsok, Bertram ;

Brand, Stephan .

AMERICAN JOURNAL OF GASTROENTEROLOGY, 2008, 103 (03) :682-691

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