title: Protective pathways against colitis mediated by appendicitis and appendectomy.
abstract: Appendicitis followed by appendectomy (AA) at a young age protects against inflammatory bowel disease (IBD). Using a novel murine appendicitis model, we showed that AA protected against subsequent experimental colitis. To delineate genes/pathways involved in this protection, AA was performed and samples harvested from the most distal colon. RNA was extracted from four individual colonic samples per group (AA group and double-laparotomy control group) and each sample microarray analysed followed by gene-set enrichment analysis (GSEA). The gene-expression study was validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR) of 14 selected genes across the immunological spectrum. Distal colonic expression of 266 gene-sets was up-regulated significantly in AA group samples (false discovery rates < 1%; P-value < 0·001). Time-course RT-PCR experiments involving the 14 genes displayed down-regulation over 28 days. The IBD-associated genes tnfsf10, SLC22A5, C3, ccr5, irgm, ptger4 and ccl20 were modulated in AA mice 3 days after surgery. Many key immunological and cellular function-associated gene-sets involved in the protective effect of AA in experimental colitis were identified. The down-regulation of 14 selected genes over 28 days after surgery indicates activation, repression or de-repression of these genes leading to downstream AA-conferred anti-colitis protection. Further analysis of these genes, profiles and biological pathways may assist in developing better therapeutic strategies in the management of intractable IBD.
authors.affiliation: Department of Medicine, St George Clinical School, University of New South Wales, Sydney, NSW, Australia. r.cheluvappa@unsw.edu.au
authors.forename: R
authors.initials: R
authors.lastname: Cheluvappa
authors.forename: A S
authors.initials: AS
authors.lastname: Luo
authors.forename: C
authors.initials: C
authors.lastname: Palmer
authors.forename: M C
authors.initials: MC
authors.lastname: Grimm
mesh_terms: D000367:Age Factors; D000818:Animals; D001062:Appendectomy; D001064:Appendicitis / Q000601:surgery*; D054418:Chemokine CCL20 / Q000235:genetics; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000517:prevention & control*; D003106:Colon / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000517:prevention & control; D053727:Interleukin-18 Receptor alpha Subunit / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010978:Platelet Factor 4 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics
chemical_list: C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; C096000:Ifi1 protein, mouse; C508573:Il18r1 protein, mouse; D053727:Interleukin-18 Receptor alpha Subunit; D053481:Secretory Leukocyte Peptidase Inhibitor; C506815:Slpi protein, mouse; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D010978:Platelet Factor 4; D019204:GTP-Binding Proteins