| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
INFLAMMATORY BOWEL DISEASE |
1 Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
2 Department of Medicine, Royal Free and University College Medical School, London, NW3 2PF, UK
3 Department of Internal Medicine and Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
4 Department of Pathology, University of Chicago Hospitals, Chicago, Illinois 60637, USA
5 The Martin Boyer Laboratories, Gastroenterology Section, Department of Medicine, University of Chicago Hospitals, Chicago, Illinois 60637, USA
Correspondence to:
Correspondence to:
Professor G Nuñez
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA; bclx{at}umich.edu
Background and aims: Genetic variation in NOD2 has been associated with susceptibility to Crohn’s disease (CD) and specifically with ileal involvement. The reason for the unique association of NOD2 mutations with ileal disease is unclear. To identify a possible link, we tested expression of NOD2 in intestinal tissue of CD patients and controls.
Patients and methods: Fifty five specimens of ileum or colon from 21 CD patients, seven ulcerative colitis (UC) patients, and five controls with pathology other than CD or UC were stained for NOD2 using an immunoperoxidase method.
Results: Using a monoclonal antibody against NOD2 developed in our laboratory, we detected uniform expression of NOD2 in terminal ileum Paneth cells from controls and patients as well as in metaplastic Paneth cells in the colon. Mechanical purification showed enriched expression of NOD2 mRNA in ileal crypts. In Paneth cells, NOD2 was located in the cytosol in close proximity to the granules that contain antimicrobial peptides. We detected minimal NOD2 in the villous epithelium of the ileum or in the colonic epithelium from both CD patients and controls.
Conclusions: These results suggest a role for NOD2 in the regulation of Paneth cell mediated responses against intestinal bacteria and a plausible mechanism to explain the selective association of NOD2 mutations with ileal disease. The impaired capacity of CD associated mutations to sense luminal bacteria may result in increased susceptibility to certain gut microbes.
Keywords: NOD2; Crohn’s disease; Paneth cell; innate immunity
Abbreviations: CD, Crohn’s disease; UC, ulcerative colitis; CARD, caspase recruitment domain; LPS, lipopolysaccharide; PGN, peptidoglycan; NF
B, nuclear factor B; RT-PCR, reverse transcription-polymerase chain reaction; PBS, phosphate buffered saline; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; TNF-
, tumour necrosis factor
Relevant Article
Gut 2003 52: 1533-1535.
This article has been cited by other articles:
|
|
 |
|
  T. Stroh, A. Batra, R. Glauben, I. Fedke, U. Erben, A. Kroesen, M. M. Heimesaat, S. Bereswill, S. Girardin, M. Zeitz, et al. Nucleotide Oligomerization Domains 1 and 2: Regulation of Expression and Function in Preadipocytes J. Immunol., September 1, 2008; 181(5): 3620 - 3627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Fishbein, G Novitskiy, L Mishra, C Matsumoto, S Kaufman, S Goyal, K Shetty, L Johnson, A Lu, A Wang, et al. NOD2-expressing bone marrow-derived cells appear to regulate epithelial innate immunity of the transplanted human small intestine Gut, March 1, 2008; 57(3): 323 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Elphick, S. Liddell, and Y. R. Mahida Impaired Luminal Processing of Human Defensin-5 in Crohn's Disease: Persistence in a Complex with Chymotrypsinogen and Trypsin Am. J. Pathol., March 1, 2008; 172(3): 702 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Wilmanski, T. Petnicki-Ocwieja, and K. S. Kobayashi NLR proteins: integral members of innate immunity and mediators of inflammatory diseases J. Leukoc. Biol., January 1, 2008; 83(1): 13 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hedl, J. Li, J. H. Cho, and C. Abraham Chronic stimulation of Nod2 mediates tolerance to bacterial products PNAS, December 4, 2007; 104(49): 19440 - 19445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Harder, R. Glaser, and J.-M. Schroder Review: Human antimicrobial proteins effectors of innate immunity Innate Immunity, December 1, 2007; 13(6): 317 - 338. [Abstract] [PDF]
|
|
|
|
|
|
G. Ferwerda, B. J. Kullberg, D. J. de Jong, S. E. Girardin, D. M. L. Langenberg, R. van Crevel, T. H. M. Ottenhoff, J. W. M. Van der Meer, and M. G. Netea Mycobacterium paratuberculosis is recognized by Toll-like receptors and NOD2 J. Leukoc. Biol., October 1, 2007; 82(4): 1011 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Sundbom, D A Elphick, Y R Mahida, R N Cunliffe, T Midtvedt, L Engstrand, C Rubio, and L G. Axelsson Alteration in human defensin-5 expression following gastric bypass surgery J. Clin. Pathol., September 1, 2007; 60(9): 1029 - 1034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lecine, S. Esmiol, J.-Y. Metais, C. Nicoletti, C. Nourry, C. McDonald, G. Nunez, J.-P. Hugot, J.-P. Borg, and V. Ollendorff The NOD2-RICK Complex Signals from the Plasma Membrane J. Biol. Chem., May 18, 2007; 282(20): 15197 - 15207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J R Korzenik Is Crohn's disease due to defective immunity? Gut, January 1, 2007; 56(1): 2 - 5. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Ansari, J Abdulla, N Zayyani, U Brahmi, S Taha, and A A Satir Comparison of RANTES expression in Crohn's disease and ulcerative colitis: an aid in the differential diagnosis? J. Clin. Pathol., October 1, 2006; 59(10): 1066 - 1072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Franchi, C. McDonald, T.-D. Kanneganti, A. Amer, and G. Nunez Nucleotide-Binding Oligomerization Domain-Like Receptors: Intracellular Pattern Recognition Molecules for Pathogen Detection and Host Defense J. Immunol., September 15, 2006; 177(6): 3507 - 3513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Keshav Paneth cells: leukocyte-like mediators of innate immunity in the intestine J. Leukoc. Biol., September 1, 2006; 80(3): 500 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Holler, G. Rogler, J. Brenmoehl, J. Hahn, H. Herfarth, H. Greinix, A. M. Dickinson, G. Socie, D. Wolff, G. Fischer, et al. Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long-term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination Blood, May 15, 2006; 107(10): 4189 - 4193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Traub, S. von Aulock, T. Hartung, and C. Hermann Invited review: MDP and other muropeptides direct and synergistic effects on the immune system Innate Immunity, April 1, 2006; 12(2): 69 - 85. [Abstract] [PDF]
|
|
|
|
|
|
E. Voss, J. Wehkamp, K. Wehkamp, E. F. Stange, J. M. Schroder, and J. Harder NOD2/CARD15 Mediates Induction of the Antimicrobial Peptide Human Beta-defensin-2 J. Biol. Chem., January 27, 2006; 281(4): 2005 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. McDonald, F. F. Chen, V. Ollendorff, Y. Ogura, S. Marchetto, P. Lecine, J.-P. Borg, and G. Nunez A Role for Erbin in the Regulation of Nod2-dependent NF-{kappa}B Signaling J. Biol. Chem., December 2, 2005; 280(48): 40301 - 40309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D A Elphick and Y R Mahida Paneth cells: their role in innate immunity and inflammatory disease Gut, December 1, 2005; 54(12): 1802 - 1809. [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Ismail and L. V. Hooper Epithelial Cells and Their Neighbors. IV. Bacterial contributions to intestinal epithelial barrier integrity Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G779 - G784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Watanabe, A Kitani, and W Strober NOD2 regulation of Toll-like receptor responses and the pathogenesis of Crohn's disease Gut, November 1, 2005; 54(11): 1515 - 1518. [Full Text] [PDF]
|
|
|
|
|
|
D A van Heel, S Ghosh, K A Hunt, C G Mathew, A Forbes, D P Jewell, and R J Playford Synergy between TLR9 and NOD2 innate immune responses is lost in genetic Crohn's disease Gut, November 1, 2005; 54(11): 1553 - 1557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Netea, G. Ferwerda, D. J. de Jong, C. Werts, I. G. Boneca, M. Jehanno, J. W. M. Van Der Meer, D. Mengin-Lecreulx, P. J. Sansonetti, D. J. Philpott, et al. The Frameshift Mutation in Nod2 Results in Unresponsiveness Not Only to Nod2- but Also Nod1-activating Peptidoglycan Agonists J. Biol. Chem., October 28, 2005; 280(43): 35859 - 35867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E Cario BACTERIAL INTERACTIONS WITH CELLS OF THE INTESTINAL MUCOSA: TOLL-LIKE RECEPTORS AND NOD2 Gut, August 1, 2005; 54(8): 1182 - 1193. [Full Text] [PDF]
|
|
|
|
|
|
D S A Sanders Mucosal integrity and barrier function in the pathogenesis of early lesions in Crohn's disease J. Clin. Pathol., June 1, 2005; 58(6): 568 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. McDonald, N. Inohara, and G. Nunez Peptidoglycan Signaling in Innate Immunity and Inflammatory Disease J. Biol. Chem., May 27, 2005; 280(21): 20177 - 20180. [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Korzenik, B. K. Dieckgraefe, J. F. Valentine, D. F. Hausman, M. J. Gilbert, and the Sargramostim in Crohn's Disease Study Group Sargramostim for Active Crohn's Disease N. Engl. J. Med., May 26, 2005; 352(21): 2193 - 2201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tanabe, T. Ayabe, B. Bainbridge, T. Guina, R. K. Ernst, R. P. Darveau, S. I. Miller, and A. J. Ouellette Mouse Paneth Cell Secretory Responses to Cell Surface Glycolipids of Virulent and Attenuated Pathogenic Bacteria Infect. Immun., April 1, 2005; 73(4): 2312 - 2320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wehkamp, M. Schmid, K. Fellermann, and E. F. Stange Defensin deficiency, intestinal microbes, and the clinical phenotypes of Crohn's disease J. Leukoc. Biol., April 1, 2005; 77(4): 460 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. T. MacDonald and G. Monteleone Immunity, Inflammation, and Allergy in the Gut Science, March 25, 2005; 307(5717): 1920 - 1925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Kobayashi, M. Chamaillard, Y. Ogura, O. Henegariu, N. Inohara, G. Nunez, and R. A. Flavell Nod2-Dependent Regulation of Innate and Adaptive Immunity in the Intestinal Tract Science, February 4, 2005; 307(5710): 731 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Gasche and P Grundtner Genotypes and phenotypes in Crohn's disease: do they help in clinical management? Gut, January 1, 2005; 54(1): 162 - 167. [Full Text] [PDF]
|
|
|
|
|
|
C. Rumio, D. Besusso, M. Palazzo, S. Selleri, L. Sfondrini, F. Dubini, S. Menard, and A. Balsari Degranulation of Paneth Cells via Toll-Like Receptor 9 Am. J. Pathol., August 1, 2004; 165(2): 373 - 381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Holler, G. Rogler, H. Herfarth, J. Brenmoehl, P. J. Wild, J. Hahn, G. Eissner, J. Scholmerich, and R. Andreesen Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation Blood, August 1, 2004; 104(3): 889 - 894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. Mathew and C. M. Lewis Genetics of inflammatory bowel disease: progress and prospects Hum. Mol. Genet., April 1, 2004; 13(90001): R161 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M C Aldhous, E R Nimmo, and J Satsangi NOD2/CARD15 and the Paneth cell: another piece in the genetic jigsaw of inflammatory bowel disease Gut, November 1, 2003; 52(11): 1533 - 1535. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
