Cathelicidin-BF, a Novel Antimicrobial Peptide from Bungarus fasciatus, Attenuates Disease in a Dextran Sulfate Sodium Model of Colitis.
Cathelicidin-BF, a Novel Antimicrobial Peptide from Bungarus fasciatus, Attenuates Disease in a Dextran Sulfate Sodium Model of Colitis.
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DOI：
10.1021/acs.molpharmaceut.5b00069
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发表时间：
2015-04
影响因子：
4.9
通讯作者：
Haiwen Zhang;Xi Xia;F. Han;Qin Jiang;Y. Rong;Deguang Song;Yizhen Wang
中科院分区：
文献类型：
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作者：
Haiwen Zhang;Xi Xia;F. Han;Qin Jiang;Y. Rong;Deguang Song;Yizhen Wang
抗菌肽是先天免疫的分子。 Cathelicidin-BF 是第一个在爬行动物中发现的 Cathelicidin 肽。然而，C-BF 的免疫调节和上皮屏障保护特性尚未见报道。炎症性肠病，包括溃疡性结肠炎和克罗恩病，可导致第三大常见恶性肿瘤结肠癌。目的是开发新发现的cathelicidin-BF 作为溃疡性结肠炎患者的治疗药物。 H&E染色观察结肠上皮形态； TUNEL法和免疫组化法检测结肠上皮细胞凋亡指数和炎症细胞浸润情况；免疫荧光法分析内源性mCRAMP的表达水平； Western blot分析结肠转录因子c-jun和NF-κB的磷酸化情况。我们的结果表明，与DSS组相比，C-BF+DSS组的结肠上皮形态有所改善。与DSS组相比，C-BF+DSS组结肠上皮炎症细胞凋亡和浸润也明显减弱，且DSS组内源性mCRAMP的表达水平显着高于其他组。 DSS 诱导 c-jun 和 NF-κB 磷酸化水平，而 C-BF 有效抑制 NF-κB (p65) 磷酸化。 C-BF的屏障保护效果依然优异。总之，C-BF 有效减轻炎症并改善受损的屏障功能。值得注意的是，这是第一份证明 C-BF 通过调节肠道免疫和保留屏障功能来减轻 DSS 诱导的 UC 的报告，并且确切的途径是通过 NF-κB。
Antimicrobial peptides are molecules of innate immunity. Cathelicidin-BF is the first cathelicidin peptide found in reptiles. However, the immunoregulatory and epithelial barrier protective properties of C-BF have not been reported. Inflammatory bowel diseases, including ulcerative colitis and Crohn's disease, can lead to colon cancer, the third most common malignant tumor. The objective is to develop the new found cathelicidin-BF as a therapeutic to patients of ulcerative colitis. The morphology of the colon epithelium was observed by H&E staining; apoptosis index and infiltration of inflammatory cells in colonic epithelium were measured by TUNEL and immunohistochemistry; the expression level of endogenous mCRAMP was analyzed by immunofluorescence; and phosphorylation of the transcription factors c-jun and NF-κB in colon were analyzed by Western blot. Our results showed that the morphology of the colon epithelium in the C-BF+DSS group was improved compared with the DSS group. Apoptosis and infiltration of inflammatory cells in colonic epithelium were also significantly attenuated in the C-BF+DSS group compared with the DSS group, and the expression level of endogenous mCRAMP in the DSS group was significantly higher than other groups. DSS-induced phosphorylation level of c-jun and NF-κB while C-BF effectively inhibited phosphorylation of NF-κB (p65). The barrier protective effect of C-BF was still excellent. In conclusion, C-BF effectively attenuated inflammation and improved disrupted barrier function. Notably, this is the first report to demonstrate that C-BF attenuates DSS-induced UC both through the regulation of intestinal immune and retention of barrier function, and the exact pathway was through NF-κB.