Rajkumar Cheluvappa1. 1. Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, NSW, Australia, rajkumarchel@gmail.com.
Abstract
BACKGROUND: Crohn's disease and ulcerative colitis are the two spectral variations of inflammatory bowel diseases (IBD). The complex interplay between genetic predisposition, gastrointestinal bacteria, and gut immunity in IBD is yet to be deciphered. The newly described IL-17-secreting subset of CD4+ T cells, called Th17 cells (and its "Th17 system"), has been increasingly implicated in the pathogenesis of inflammatory changes in inflammatory/autoimmune diseases including IBD. The chemokine ligand CCL20 and its receptor CCR6 are both upregulated in colon biopsy samples during active IBD. Appendicitis and appendectomy (AA) prevents or significantly ameliorates human IBD. METHODS: We pioneered the first animal model of AA. AA was performed on 5-week-old male BALB/c mice, and distal-colon samples were harvested. Mice with two laparotomies each served as sham and sham (SS) controls. RNA was extracted from individual colonic replicate samples (AA and SS groups) and each sample microarray analyzed and reverse transcription-polymerase chain reaction (RT-PCR) validated. Gene set enrichment analysis (GSEA) software was used to further analyze the microarray data. RESULTS: Prior AA ameliorates experimental colitis in our murine model. CCL20 expression was significantly suppressed (along with components of the Th17 system) in the most distal colon 3 and 28 days after AA was done at the most proximal colon. CONCLUSION: Teasing out the pathways involved in the changes induced by AA on the colon in clinical studies and, most importantly, in our unique murine AA model will lead to the development of techniques to manipulate different components of the CCL20-CCR6 axis and Th17 system resulting in significant advances in IBD management.
BACKGROUND:Crohn's disease and ulcerative colitis are the two spectral variations of inflammatory bowel diseases (IBD). The complex interplay between genetic predisposition, gastrointestinal bacteria, and gut immunity in IBD is yet to be deciphered. The newly described IL-17-secreting subset of CD4+ T cells, called Th17 cells (and its "Th17 system"), has been increasingly implicated in the pathogenesis of inflammatory changes in inflammatory/autoimmune diseases including IBD. The chemokine ligand CCL20 and its receptor CCR6 are both upregulated in colon biopsy samples during active IBD. Appendicitis and appendectomy (AA) prevents or significantly ameliorates human IBD. METHODS: We pioneered the first animal model of AA. AA was performed on 5-week-old male BALB/c mice, and distal-colon samples were harvested. Mice with two laparotomies each served as sham and sham (SS) controls. RNA was extracted from individual colonic replicate samples (AA and SS groups) and each sample microarray analyzed and reverse transcription-polymerase chain reaction (RT-PCR) validated. Gene set enrichment analysis (GSEA) software was used to further analyze the microarray data. RESULTS: Prior AA ameliorates experimental colitis in our murine model. CCL20 expression was significantly suppressed (along with components of the Th17 system) in the most distal colon 3 and 28 days after AA was done at the most proximal colon. CONCLUSION: Teasing out the pathways involved in the changes induced by AA on the colon in clinical studies and, most importantly, in our unique murine AA model will lead to the development of techniques to manipulate different components of the CCL20-CCR6 axis and Th17 system resulting in significant advances in IBD management.
Authors: Richard H Duerr; Kent D Taylor; Steven R Brant; John D Rioux; Mark S Silverberg; Mark J Daly; A Hillary Steinhart; Clara Abraham; Miguel Regueiro; Anne Griffiths; Themistocles Dassopoulos; Alain Bitton; Huiying Yang; Stephan Targan; Lisa Wu Datta; Emily O Kistner; L Philip Schumm; Annette T Lee; Peter K Gregersen; M Michael Barmada; Jerome I Rotter; Dan L Nicolae; Judy H Cho Journal: Science Date: 2006-10-26 Impact factor: 47.728
Authors: M G Russel; E Dorant; R J Brummer; M A van de Kruijs; J W Muris; J M Bergers; J Goedhard; R W Stockbrügger Journal: Gastroenterology Date: 1997-08 Impact factor: 22.682