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在实验性结核病中 N-甲酰化肽 的免疫治疗潜力。

Immunotherapeutic potential of an N-formylated peptide of in experimental tuberculosis.

机构信息

a Department of Biochemistry , Postgraduate Institute of Medical Education & Research (PGIMER) , Chandigarh , India.

b Department of Medical Laboratory Sciences, College of Applied Medical Science , Majmaah University , Al Majmaah , Saudi Arabia.

出版信息

Immunopharmacol Immunotoxicol. 2019 Apr;41(2):292-298. doi: 10.1080/08923973.2019.1593446. Epub 2019 May 3.

Abstract

The current therapeutic regimens for tuberculosis (TB) are complex and involve the prolonged use of multiple antibiotics with diverse side effects that lead to therapeutic failure and bacterial resistance. The standard appliance of immunotherapy may aid as a powerful tool to combat the ensuing threat of TB. We have earlier reported the immunotherapeutic potential of N-formylated peptides of two secretory proteins of HRv. Here, we investigated the immunotherapeutic effect of an N-formylated peptide from in experimental TB. The N-terminally formylated listerial peptide with amino acid sequence 'f-MIGWII' was tested for its adjunctive therapeutic efficacy in combination with anti-tuberculosis drugs (ATDs) in the mouse model of TB. In addition, its potential to generate reactive oxygen species (ROS) in murine neutrophils was also evaluated The LemA peptide (f-MIGWII) induced a significant increase in the intracellular ROS levels of mouse neutrophils ( ≤ .05). The ATD treatment reduced the colony forming units (CFU) in lungs and spleen of infected mice by 2.39 and 1.67 log units, respectively ( < .001). Treatment of the infected mice with combination of ATDs and LemA peptide elicited higher therapeutic efficacy over ATDs alone. The histopathological changes in the lungs of infected mice also correlated well with the CFU data. Our results clearly indicate that LemA peptide conferred an additional therapeutic effect when given in combination with the ATDss ( < .01) and hence can be used as adjunct to the conventional chemotherapy against TB

摘要

目前的结核病(TB)治疗方案较为复杂,需要长期使用多种具有不同副作用的抗生素,这导致治疗失败和细菌耐药性的产生。免疫疗法的标准应用可能是对抗 TB 威胁的有力工具。我们之前已经报道了 HRv 的两种分泌蛋白的 N-甲酰化肽的免疫治疗潜力。在这里,我们研究了 中的 N-甲酰化肽在实验性 TB 中的免疫治疗效果。具有氨基酸序列“f-MIGWII”的 N-端甲酰化李斯特菌肽被测试与抗结核药物(ATD)联合使用在 TB 小鼠模型中的辅助治疗效果。此外,还评估了其在鼠中性粒细胞中产生活性氧物种(ROS)的潜力。 LemA 肽(f-MIGWII)诱导鼠中性粒细胞内 ROS 水平显著增加(≤.05)。ATD 治疗使感染小鼠肺部和脾脏中的菌落形成单位(CFU)分别减少 2.39 和 1.67 对数单位(<.001)。与单独使用 ATD 相比,用 ATD 和 LemA 肽联合治疗感染小鼠可产生更高的治疗效果。感染小鼠肺部的组织病理学变化与 CFU 数据也很好地相关。我们的结果清楚地表明,当 LemA 肽与 ATD 联合使用时,可提供额外的治疗效果(<.01),因此可作为抗结核常规化疗的辅助手段。

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