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外源性鼠抗菌肽 CRAMP 显著加重卵清蛋白诱导的气道炎症,但改善 BALB/c 小鼠的 2,4-二硝基氟苯诱导的结肠炎。

Exogenous murine antimicrobial peptide CRAMP significantly exacerbates Ovalbumin-induced airway inflammation but ameliorates oxazolone-induced intestinal colitis in BALB/c mice.

机构信息

a Laboratory of Molecular Immunology , Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College , Kunming , China.

b Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases , Kunming , China.

出版信息

Hum Vaccin Immunother. 2018 Jan 2;14(1):146-158. doi: 10.1080/21645515.2017.1386823. Epub 2017 Nov 29.

Abstract

Cathelicidin has been reported to be multifunctional. The current study aimed to investigate the influences of exogenous cathelicidin-related antimicrobial peptide (CRAMP) on inflammatory responses in different disease models. In OVA-induced allergic airway inflammation, CRAMP significantly enhanced the infiltration of inflammatory cells and accumulation of proinflammatory Th2 cytokine IL-13 and IL-33 in bronchial alveolar lavage fluid (BALF), exacerbated lung tissue inflammation and airway goblet cell hyperplasia, and elevated OVA-specific IgE level in serum. In oxazolone-induced intestinal colitis, the expression levels of CRAMP and its receptor FPR2 significantly increased in comparison with those of TNBS-induced mice, vesicle and normal controls. Exogenous CRAMP significantly prevented the development of ulcerative colitis, evidenced by improved body weight regain, decreased colons weight/length ratio, elevated epithelial integrity, and ameliorated colon tissue inflammation. In addition, pro-inflammatory cytokines TNF-α, IL-1β, IL-4 and IL-13, as well as chemokines CXCL2 and CXCL5 for neutrophils recruitment were significantly decreased in CRAMP-treated mice, and epithelial repair-related factors MUC2 and Claudin1 were increased, determined by real time-PCR and ELISAs. The results indicated that although CRAMP has pro-inflammatory effects in airway, local application of exogenous CRAMP might be a potential approach for the treatment of ulcerative colitis.

摘要

抗菌肽 cathelicidin 具有多功能性。本研究旨在探讨外源性抗菌肽相关抗菌肽(CRAMP)在不同疾病模型中的炎症反应的影响。在 OVA 诱导的过敏性气道炎症中,CRAMP 显著增强了支气管肺泡灌洗液(BALF)中炎症细胞的浸润和促炎 Th2 细胞因子 IL-13 和 IL-33 的积累,加重了肺组织炎症和气道杯状细胞增生,并提高了血清中 OVA 特异性 IgE 水平。在 Oxazolone 诱导的结肠炎中,CRAMP 及其受体 FPR2 的表达水平与 TNBS 诱导的小鼠、囊泡和正常对照组相比显著增加。外源性 CRAMP 显著预防了溃疡性结肠炎的发展,这表现在体重恢复增加、结肠重量/长度比降低、上皮完整性提高和结肠组织炎症减轻。此外,在 CRAMP 治疗的小鼠中,促炎细胞因子 TNF-α、IL-1β、IL-4 和 IL-13 以及招募中性粒细胞的趋化因子 CXCL2 和 CXCL5 显著减少,实时 PCR 和 ELISA 测定表明上皮修复相关因子 MUC2 和 Claudin1 增加。结果表明,尽管 CRAMP 在气道中具有促炎作用,但局部应用外源性 CRAMP 可能是治疗溃疡性结肠炎的一种潜在方法。

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