人抗菌肽LL-37在溃疡性结肠炎组织中的表达及其与结肠炎症的关系  

Correlation between expression of human cathelicidin peptide LL-37 and colon inflammation in patients with ulcerative colitis

作　　者：李懿璇[1] 王化虹[1] 迟雁[1] 

机构地区：[1]北京大学第一医院消化内科,北京市100034

出　　处：《世界华人消化杂志》2011年第13期1359-1366,共8页World Chinese Journal of Digestology

摘　　要：目的:探讨LL-37在溃疡性结肠炎(UC)患者结肠黏膜组织中的表达及其与结肠炎症之间的关系.方法:选择2007-09/2008-12在北京大学第一医院消化内科确诊的UC患者32例,并按UC疾病活动指数(UCDAI)分为轻、中、重度活动组;选择同时期行结肠镜发现有结肠息肉的患者为对照组;用荧光定量PCR方法测定不同疾病活动度UC患者的炎症结肠黏膜中LL-37和炎症因子(TNF-α、IL-1β、IL-4)的表达及其相互关系;用免疫组织化学方法观察LL-37在正常结肠黏膜和炎症黏膜中的表达部位;用炎症因子体外刺激结肠上皮细胞,观察其对LL-37表达的影响.结果:活动期UC患者炎症结肠黏膜中LL-37和炎症因子的表达较正常黏膜增高(LL-37:4.97±6.95,31.46±10.74,75.50±13.19vs0.27±0.45;TNF-α:97.04±23.74,201.07±33.46,290.81±30.45vs72.82±18.85;IL-1β:72.98±38.03,153.46±22.68,211.34±25.12vs38.56±10.38;IL-4:26.04±12.47,46.38±15.12,46.94±16.53vs19.34±11.61,均P<0.05),且随疾病活动度的增加而增高,二者的表达呈正相关(γ=0.965,0.940,0.628,均P<0.01);LL-37表达于人正常结肠黏膜和UC患者炎症结肠黏膜的表层上皮,另外在UC患者炎症黏膜中浸润的大量炎症细胞内存在高表达;体外炎症因子刺激并不能上调结肠上皮细胞中LL-37的表达.结论:抗菌肽LL-37在活动期UC患者炎症结肠黏膜中的高表达及其与炎症因子呈正相关,提示其参与了UC的免疫炎症过程,但其机制可能与结肠上皮细胞无关.AIM：To investigate the expression of human cathelicidin LL-37 in the colon mucosa of patients suffering from ulcerative colitis and to assess its relationship with colon inflammation.METHODS：Thirty-two patients with ulcerative colitis were included in the study.The severity of ulcerative colitis was assessed using the Ulcerative Colitis Disease Activity Index（UCDAI）.The expression of LL-37 and cytokines（TNF-α,IL-1βand IL-4）in the colon mucosa was detected by real-time RT-PCR.Immunohistochemistry was used to investigate the location of the LL-37 peptide in the normal and inflamed colon mucosa.Colon epithelial cells were stimulated in vitro with cytokines to evaluate mechanisms that influence cathelicidin production.RESULTS：The mRNA expression of LL-37 and cytokines in the colon mucosa was significantly elevated with the severity of disease activity in UC patients compared to controls（LL-37：4.97 ±6.95,31.46±10.74,75.50±13.19 vs 0.27±0.45;TNF-α：97.04±23.74,201.07±33.46,290.81± 30.45 vs 72.82±18.85;IL-1β：72.98±38.03,153.46 ±22.68,211.34±25.12 vs 38.56±10.38;IL-4：26.04 ±12.47,46.38±15.12,46.94±16.53 vs 19.34± 11.61,all P0.05）.Significant correlations were found between the mRNA expression of LL-37 and cytokines（r=0.965,0.940,0.628,all P0.01）.Immunohistochemistry analysis showed that the LL-37 peptide was located in the colon epithelial surface in both normal controls and UC patients.In addition,the LL-37 peptide was detected easily in inflammatory cells infiltrating into the inflamed colon mucosa in UC patients.In vitro stimulation with cytokines did not up-regulate LL-37 expression in colon epithelial cells.CONCLUSION：The up-regulation of LL-37 expression in inflamed colon mucosa of UC patients and high correlation between the expression of LL-37 and cytokines indicate a close relationship between LL-37 and immune inflammatory response in UC patients with ulcerative colitis;however,this process does not involve colonic epithelial cells.

关 键 词：溃疡性结肠炎 抗菌肽LL-37 炎症因子 

分 类 号：R574.62[医药卫生—消化系统]