Reduced -defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn's disease
| Autor: | Michael Walsh, Graham L. Radford-Smith, Lisa A. Simms, James D. Doecke, Elizabeth V. Fowler, Ning Huang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Paneth Cells alpha-Defensins medicine.medical_specialty Genotype Nod2 Signaling Adaptor Protein Gene Expression Inflammation Ileum Group II Phospholipases A2 digestive system Gastroenterology Article Alpha defensin Proinflammatory cytokine Immunoenzyme Techniques Crohn Disease NOD2 Internal medicine Humans Medicine RNA Messenger Defensin Aged Crohn's disease Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction business.industry digestive oral and skin physiology Interleukin-8 Middle Aged medicine.disease digestive system diseases medicine.anatomical_structure Paneth cell Immunology Female Muramidase medicine.symptom business |
| Zdroj: | Gut. 57:903-910 |
| ISSN: | 0017-5749 |
| Popis: | Reduced ileal Paneth cell alpha-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, alpha-defensins and Crohn's disease are linked.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.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, p0.001; DEFA6, p = 0.001). In contrast to previous studies, we found no significant association between alpha-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.Reduction in alpha-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. |
| Databáze: | OpenAIRE |
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