Szebeni B, Veres G, Dezsõfi A, Rusai K, Vannay A, Mraz M, Majorova E, Arató A
First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Clin Exp Immunol. 2008 Jan;151(1):34-41. doi: 10.1111/j.1365-2249.2007.03531.x. Epub 2007 Nov 7.
Inflammatory bowel disease (IBD) may result from exaggerated stimulation of the mucosal immune system by luminal bacterial flora. Bacterial products are recognized by pattern recognition receptors such as Toll-like receptors (TLRs), which are key regulators of the innate immune system. Therefore, the expression of TLR2, TLR3 and TLR4 in colonic biopsy samples taken from children with active IBD were studied and compared to controls. Colonic biopsy samples were collected from macroscopically inflamed and non-inflamed regions of the mucosa of 12 children with freshly diagnosed IBD (fdIBD) and 23 children with relapsed IBD (rIBD). Specimens were also obtained from eight controls. TLR2, TLR3 and TLR4 mRNA expression and protein levels were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot. We found higher TLR2 and TLR4 mRNA and protein levels in the inflamed colonic mucosa of children with fdIBD and rIBD compared to controls. In the non-inflamed colonic mucosa of children with fdIBD and rIBD, TLR2 and TLR4 mRNA and protein levels were similar to controls. TLR2 and TLR4 mRNA and protein levels also did not differ between children with fdIBD or rIBD in either inflamed or non-inflamed colonic mucosa. TLR3 mRNA expression and protein levels were similar in all groups studied. Our results of increased levels of TLR2 and TLR4 in the inflamed colonic mucosa of children with IBD confirm the hypothesis that innate immunity has an important role in the pathogenesis of this disease.
炎症性肠病(IBD)可能是由于管腔细菌菌群对黏膜免疫系统的过度刺激所致。细菌产物可被Toll样受体(TLR)等模式识别受体识别,这些受体是先天性免疫系统的关键调节因子。因此,研究了从患有活动性IBD的儿童获取的结肠活检样本中TLR2、TLR3和TLR4的表达,并与对照组进行比较。从12名新诊断为IBD(fdIBD)的儿童和23名复发IBD(rIBD)的儿童的黏膜宏观炎症和非炎症区域采集结肠活检样本。还从8名对照者获取样本。通过实时逆转录聚合酶链反应(RT-PCR)和蛋白质印迹法测定TLR2、TLR3和TLR4的mRNA表达和蛋白水平。我们发现,与对照组相比,fdIBD和rIBD儿童炎症性结肠黏膜中的TLR2和TLR4 mRNA及蛋白水平更高。在fdIBD和rIBD儿童的非炎症性结肠黏膜中,TLR2和TLR4 mRNA及蛋白水平与对照组相似。在炎症性或非炎症性结肠黏膜中,fdIBD或rIBD儿童之间的TLR2和TLR4 mRNA及蛋白水平也无差异。在所有研究组中,TLR3 mRNA表达和蛋白水平相似。我们关于IBD儿童炎症性结肠黏膜中TLR2和TLR4水平升高的结果证实了先天性免疫在该疾病发病机制中起重要作用这一假说。