Teng Xu, Xu Ling-Fen, Zhou Ping, Sun Hong-Wei, Sun Mei
Department of Pediatric Gastroenterology, Shengjing Hospital Of China Medical University, Shenyang, 110004, Liaoning, China.
Inflammation. 2009 Apr;32(2):120-9. doi: 10.1007/s10753-009-9110-x.
The trefoil factor (TFF) peptides are major secretory products of mucus cells of the gastrointestinal tract. There were evidences that administration of recombinant human TFF3 is effective in treatment of models of colitis, but the mechanism of the effects of rTFF3 is not fully understood. The main aims of this study is to evaluate effects of intraperitoneal injection recombinant human TFF3 on the expression of tumour necrosis factor alpha (TNF-alpha), toll-like receptor 4(TLR4), and nuclear factor kappaB (NF-kappaB) in trinitrobenzene sulphonic acid (TNBS) induced colitis mice. Distal colitis was induced in BALB/C mice by intracolonic administration of TNBS in ethanol. Treated with administration rhTFF3 for treatment group(5 mg/ml; approximately 0.5 mg/mouse), and normal saline for control for 5 consecutive days. Colonic damage score, tissue myeloperoxidase (MPO) activity, TLR4, NF-kappaB mRNA expression, and tissue TNF-alpha, TLR4, NF-kappaB production were determined, respectively. Once daily application of hTFF3 for 5 days after TNBS/ethanol had been injected, both microscopic and macroscopic injury and inflammatory index had been reduced compared with controls. In addition, decreased tissue TNF-alpha, TLR4, NF-kappaB production, and TLR4, NF-kappaB mRNA expression had been found. This study has shown that hTFF3 may have therapeutic potential in the treatment of inflammatory bowel disease, and one of the mechanisms may related to inhibit the TLR4/NF-kappaB signaling pathways.
三叶因子（TFF）肽是胃肠道黏液细胞的主要分泌产物。有证据表明，给予重组人TFF3对结肠炎模型的治疗有效，但rTFF3作用的机制尚未完全阐明。本研究的主要目的是评估腹腔注射重组人TFF3对三硝基苯磺酸（TNBS）诱导的结肠炎小鼠中肿瘤坏死因子α（TNF-α）、Toll样受体4（TLR4）和核因子κB（NF-κB）表达的影响。通过在乙醇中向BALB/C小鼠结肠内注射TNBS诱导远端结肠炎。治疗组用rhTFF3（5mg/ml；约0.5mg/小鼠）给药治疗，对照组用生理盐水连续给药5天。分别测定结肠损伤评分、组织髓过氧化物酶（MPO）活性、TLR4、NF-κB mRNA表达以及组织TNF-α、TLR4、NF-κB的产生。在注射TNBS/乙醇后，每天应用hTFF3一次，持续5天，与对照组相比，显微镜和肉眼可见的损伤以及炎症指数均降低。此外，还发现组织TNF-α、TLR4、NF-κB的产生以及TLR4、NF-κB mRNA表达均下降。本研究表明，hTFF3在治疗炎症性肠病方面可能具有治疗潜力，其机制之一可能与抑制TLR4/NF-κB信号通路有关。
