Tai Emily K K, Wu William K K, Wong Helen P S, Lam Emily K Y, Yu L, Cho C H
Department of Pharmacology, The University of Hong Kong, Hong Kong, China.
Exp Biol Med (Maywood). 2007 Jun;232(6):799-808.
Cathelicidin, an antimicrobial peptide of the innate immune system, modulates microbial growth, wound healing, and inflammation. However, its association with inflammatory bowel diseases (IBDs) is unknown. Our objective was to determine whether cathelicidin would exert a modulatory effect on the progression of IBD and, if so, investigate the mechanism of action through which this effect occurred. We evaluated the potential for a synthetic cathelicidin, the mouse cathelin-related antimicrobial peptide (mCRAMP), to prevent the initiation and promote the healing of lesions from inflammatory colitis that was experimentally induced in mice with dextran sulfate sodium (DSS). During the experiment, mCRAMP was given: (i) as a parallel treatment starting together with 3% DSS feeding, and (ii) as a posttreatment starting 7 days after 3% DSS feeding. The body weight, fecal microflora populations, clinical symptoms, and histologic findings of colonic tissues were measured. Relative gene expression of mucins (MUC1, MUC2, MUC3, and MUC4) in colonic tissues was determined by real-time polymerase chain reaction. Intrarectal administration of mCRAMP ameliorated DSS-induced colitis with negligible effects on mucosal healing. The peptide also significantly reduced the increased number of fecal microflora in colitis animals. It reversed the decline of colonic mucus thickness during colitis through upregulation of the expression of mucin genes. Treatment with mCRAMP also prevented colitis development by suppressing the induction of apoptosis by DSS. The current study demonstrates for the first time that intrarectal administration of cathelicidin may be a novel therapeutic option for IBDs.
cathelicidin是一种先天性免疫系统的抗菌肽，可调节微生物生长、伤口愈合和炎症反应。然而，其与炎症性肠病（IBD）的关联尚不清楚。我们的目的是确定cathelicidin是否会对IBD的进展产生调节作用，如果是，则研究这种作用发生的作用机制。我们评估了一种合成的cathelicidin，即小鼠cathelin相关抗菌肽（mCRAMP），预防葡聚糖硫酸钠（DSS）诱导的小鼠实验性炎症性结肠炎病变的起始并促进其愈合的潜力。在实验过程中，给予mCRAMP：（i）作为与3% DSS喂养同时开始的平行治疗，以及（ii）作为在3% DSS喂养7天后开始的后期治疗。测量了体重、粪便微生物菌群数量、临床症状以及结肠组织的组织学发现。通过实时聚合酶链反应测定结肠组织中粘蛋白（MUC1、MUC2、MUC3和MUC4）的相对基因表达。直肠内给予mCRAMP可改善DSS诱导的结肠炎，对黏膜愈合的影响可忽略不计。该肽还显著减少了结肠炎动物粪便微生物菌群数量的增加。它通过上调粘蛋白基因的表达逆转了结肠炎期间结肠黏液厚度的下降。mCRAMP治疗还通过抑制DSS诱导的细胞凋亡来预防结肠炎的发展。当前研究首次证明直肠内给予cathelicidin可能是IBD的一种新型治疗选择。
