Department of Medicine, St George Clinical School, University of New South Wales, Sydney, NSW, Australia.
Clin Exp Immunol. 2011 Sep;165(3):393-400. doi: 10.1111/j.1365-2249.2011.04434.x. Epub 2011 Jun 27.
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.
年轻时行阑尾切除术（AA）切除阑尾可预防炎症性肠病（IBD）。我们使用一种新的小鼠阑尾炎模型表明，AA 可预防随后发生的实验性结肠炎。为了阐明涉及这种保护的基因/途径，对 AA 进行了操作，并从最远端结肠采集样本。从每组（AA 组和双剖腹手术对照组）的四个个体结肠样本中提取 RNA，并对每个样本进行微阵列分析，然后进行基因集富集分析（GSEA）。通过对免疫谱中 14 个选定基因的定量逆转录-聚合酶链反应（RT-PCR）对基因表达研究进行了验证。AA 组样本中 266 个基因集的远端结肠表达显著上调（错误发现率<1%；P 值<0.001）。涉及 14 个基因的时间过程 RT-PCR 实验显示，28 天后下调。IBD 相关基因 tnfsf10、SLC22A5、C3、ccr5、irgm、ptger4 和 ccl20 在手术后 3 天在 AA 小鼠中被调节。在实验性结肠炎中，AA 的保护作用涉及许多关键的免疫和细胞功能相关基因集，这些基因集的表达被确定。手术后 28 天内 14 个选定基因的下调表明这些基因的激活、抑制或去抑制，从而导致下游 AA 赋予抗结肠炎保护。对这些基因、谱和生物途径的进一步分析可能有助于开发治疗难治性 IBD 的更好治疗策略。
