TITLE

Reduced α-defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn's disease

AUTHOR(S)
Simms, L. A.; Doecke, J. D.; Walsh, M. D.; Huang, N.; Fowler, E. V.; Radford-smith, G. L.
PUB. DATE
July 2008
SOURCE
Gut;Jul2008, Vol. 57 Issue 7, p903
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: Reduced heal Paneth cell α- defensin expression has been reported to be associated with Crohn's disease, especially in patients carrying NOD2 mutations. The aim of this study was to independently assess whether NOD2, α-defensins and Crohn's disease are linked. Methods: Using quantitative real-time polymerase chain reaction (RT-PCR), we measured the mRNA expression levels of key Paneth cell antimicrobial peptides (DEFA5, DEFA6, LYZ, PLA2G2A(, inflammatory cytokines [interkelukin 6 (IL6) and IL8], and a marker of epithelial cell content, villin (VIL1) in 106 samples from both affected ileum (inflamed Crohn's disease cases, n = 44) and unaffected ileum (non-inflamed; Crohn's disease cases, n = 51 and controls, n = 11). Anti-human defensin 5 (HD- 5) and haematoxylin/eosin immunohistochemical staining was performed on parallel sections from NOD2 wild-type and NOD2 mutant ileal Crohn's disease tissue. Results: In Crohn's disease patients, DEFA5 and DEFA6 mRNA expression levels were 1.9- and 2.2-fold lower, respectively, in histologically confirmed inflamed ileal mucosa after adjustment for confounders (DEFA5, p<0.001; DEFA6, p = 0.001). In contrast to previous studies, we found no significant association between α-defensin expression and NOD2 genotype. HD-5 protein data supports these RNA findings. The reduction in HD-5 protein expression appears due to surface epithelial cell loss and reduced Paneth cell numbers as a consequence of tissue damage. Conclusions: Reduction in α-defensin expression is independent of NOD2 status and is due to loss of surface epithelium as a consequence of inflammatory changes rather than being the inciting event prior to inflammation in ileal Crohn's disease.
ACCESSION #
32894054

 

Related Articles

  • Effect of X Radiation on Rat Fetal Oral Mucosa in Tissue Culture. BRACHO, MIGUEL A.; ROSE, GEORGE G.; CATTONI, MARTIN; NIKAI, HIROMASA // Journal of Dental Research;Jul1970, Vol. 49 Issue 4, p852 

    Cultures of oral mucosa from 15- to 17- day-old rat fetuses were placed under cellophane membranes on cover glasses of Rose chambers to determine the action of low doses of X radiation on the oral epithelial cells, exclusive of mitotic phenomena. The principal characteristic of the emigrating...

  • Experimental caprine coccidiosis caused by Eimeria arloingi: Morphopathologic and electron microscopic studies. Hashemnia, Mohammad; Khodakaram-Tafti, Azizollah; Razavi, Seyed; Nazifi, Saeed // Veterinary Research Communications;Mar2012, Vol. 36 Issue 1, p47 

    The progressive morphohistopathologic changes, distribution pattern of lesions and ultrastructural characteristics in Eimeria arloingi infection were investigated in experimentally infected kids. The 18 newborn animals allocated to 3 equal groups. Two of groups, A, B were inoculated with a...

  • Ca2+ influx through the basolateral- and luminal membranes of colonic epithelium in neonatal rats. Soo Jeong Kim; Joo Hyun Nam; Ji-Eun Woo; Sung Joon Kim; Poong Lyul Rhee // Pflugers Archiv European Journal of Physiology;Jan2004, Vol. 447 Issue 4, p408 

    In this study, the short-circuit currents (Isc) of electrolyte absorption and secretion in neonatal and adult rat colonic mucosa were compared and the role of Ca2+ influx through luminal membranes examined in relation to the replenishment of intracellular Ca2+ stores in colonic crypt cells....

  • Role of Meprins to Protect Ileal Mucosa of Crohn's Disease Patients from Colonization by Adherent-Invasive E. coli. Vazeille, Emilie; Bringer, Marie-Agnés; Gardarin, Aurélie; Chambon, Christophe; Becker-Pauly, Christoph; Pender, Sylvia L. F.; Jakob, Christine; Müller, Stefan; Lottaz, Daniel; Darfeuille-Michaud, Arlette // PLoS ONE;2011, Vol. 6 Issue 6, p1 

    Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to adhere to and invade intestinal epithelial cells (IEC), and to survive within macrophages. The interaction of AIEC with IEC depends on bacterial factors mainly type 1...

  • Genotypic Characterization of an Epithelial Cell Line for the Study of Parasite-Epithelial Interactions. Buret, Andre; Yi-Chan Lin // Journal of Parasitology;Apr2008, Vol. 94 Issue 2, p545 

    The findings discussed in the present research note report the extensive genotypic characterization of an intestinal epithelial cell line originally obtained from a human patient. Although the line exhibits karyotypic anomalies, with 76 modal chromosomes, its immunological, biochemical, and...

  • Structural Modification of the Gastrointestinal Epithelium during Immune-Dependent Granulomatosis. Nepomnyashchikh, D. L.; Burkovskaya, V. A.; Aidagulova, S. V.; Bakarev, M. A.; Postnikova, O. A.; Kapustina, V. I.; Nokhrina, Zh. V.; Vinogradova, E. V. // Bulletin of Experimental Biology & Medicine;Feb2011, Vol. 150 Issue 4, p490 

    We present results of pathomorphological study of the mucosa epithelium in various parts of the gastrointestinal tract in Crohn's disease. Particular attention was paid to structural transformation of epithelial cells. Barrier dysfunction of the gastrointestinal mucosa was shown to be one of the...

  • EXPRESSION OF NOD2 BY INTESTINAL EPITHELIAL CELLS IN AN IN VITRO M CELL MODEL. Butler, M.; Winstanley, S.; van Heel, D.; Lombardi, G.; Lechler, R.; Playford, R.; Ghosh, S. // Gut;Apr2004 Supplement 3, Vol. 53, pA64 

    The article cites a study on the expression of NOD2 by intestinal epithelial cells in an in vitro M cell model. NOD2 is a cytosolic detector of peptidoglycans-specifically muramyl dipeptides (MDP)—and is principally expressed by cells of the myeloid lineage (monocytes, macrophages and...

  • Adherent-Invasive Escherichia coli: Role in Crohn's Disease Pathogenesis. Darfeuille-Michaud, Arlette // Inflammatory Bowel Disease Monitor;Jul2009, Vol. 10 Issue 3, p77 

    In addition to NOD2 mutations, recent genome-wide association studies have highlighted mutations in ATG16L1 and IRGM as being associated with Crohn's disease risk. Given the intracellular location of NOD2 and the role of ATG16L1 and IRGM in autophagy, the presence of pathogenic invasive bacteria...

  • Choline Acetyltransferase, Acetylcholinesterase, and Nicotinic Acetylcholine Receptors of Human Gingival and Esophageal Epithelia. Thuong Nguyen, V.; Hall, L. L.; Gallacher, G.; Ndoye, A.; Jolkovsky, D. L.; Webber, R. J.; Buchli, R.; Grando, S. A. // Journal of Dental Research;Apr2000, Vol. 79 Issue 4, p939 

    A non-neuronal cholinergic system that includes neuronal-like nicotinic acetylcholine receptors (nAChRs) has recently been described in epithelial cells that line the skin and the upper respiratory tract. Since the use of nicotine-containing products is associated with morbidity in the upper...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics