Frolova Lenka, Drastich Pavel, Rossmann Pavel, Klimesova Klara, Tlaskalova-Hogenova Helena
Department of Immunology and Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
J Histochem Cytochem. 2008 Mar;56(3):267-74. doi: 10.1369/jhc.7A7303.2007. Epub 2007 Nov 26.
Dysregulation of innate and adaptive intestinal immune responses to bacterial microbiota is supposed to be involved in pathogenetic mechanisms of inflammatory bowel diseases (IBDs). We investigated expression of Toll-like receptor 2 (TLR2), TLR4, and their transmembrane coreceptor CD14 in biopsy samples from patients with IBD and in non-inflamed gut mucosa from controls. Small intestine and colon samples were obtained by colonoscopy from patients with Crohn's disease (CD), ulcerative colitis (UC), and controls. Immunohistochemical analysis of cryostat sections using polyclonal and monoclonal antibodies specific for TLR2, TLR4, and CD14 showed a significant increase in TLR2 expression in the terminal ileum of patients with inactive and active UC against controls. Significant upregulation of TLR4 expression relative to controls was found in the terminal ileum and rectum of UC patients in remission and in the terminal ileum of CD patients with active disease. CD14 expression was upregulated in the terminal ileum of CD patients in remission and with active disease, in the cecum of UC patients in remission and with active disease, and in rectum of UC patients with active disease. Hence, dysregulation of TLR2, TLR4, and CD14 expression in different parts of the intestinal mucosa may be crucial in IBD pathogenesis.
肠道对细菌微生物群的先天性和适应性免疫反应失调被认为参与了炎症性肠病(IBD)的发病机制。我们研究了IBD患者活检样本以及对照的非炎症性肠黏膜中Toll样受体2(TLR2)、TLR4及其跨膜共受体CD14的表达。通过结肠镜检查从克罗恩病(CD)、溃疡性结肠炎(UC)患者及对照获取小肠和结肠样本。使用针对TLR2、TLR4和CD14的多克隆和单克隆抗体对冰冻切片进行免疫组织化学分析,结果显示,与对照相比,静止期和活动期UC患者回肠末端的TLR2表达显著增加。在缓解期UC患者的回肠末端和直肠以及活动期CD患者的回肠末端发现TLR4表达相对于对照显著上调。缓解期和活动期CD患者的回肠末端、缓解期和活动期UC患者的盲肠以及活动期UC患者的直肠中CD14表达上调。因此,肠黏膜不同部位TLR2、TLR4和CD14表达失调可能在IBD发病机制中起关键作用。