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A Synthetic Peptide 2Abz 23 S 29 Reduces Bacterial Titer and Induces Pro-Inflammatory Cytokines in a Murine Model of Urinary Tract Infection

机译:合成肽2abz 23s 29减少细菌滴度,并在尿路感染的小鼠模型中诱导促炎细胞因子

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Introduction: A urinary tract infection (UTI), which is often caused by uropathogenic E. coli (UPEC) strains, affects many people worldwide annually. UPEC causes the production of pro-inflammatory cytokines by the bladder epithelial cells; however, it has been proven that the UPEC can inhibit the early activation of the innate immune system. Methods: This study aimed to examine the antibacterial and immunomodulatory effects of different doses of truncated alpha-defensins (human neutrophil peptide (HNP)-1) analog 2Abz23S29 on the mouse UTI model. Experimentally uropathogenic E. coli CFT073-infected mice were treated with low-dose 2Abz23S29 (250μg/mL), high-dose 2Abz23S29 (750μg/mL), ciprofloxacin (cip) (800μg/mL), or high-dose 2Abz23S29plus cip once a day 24 h post-infection. The 2Abz23S29 and cip treatment were given for two consecutive days. Results: The in vivo results showed that fewer UPEC were recovered from the bladders of mice treated transurethrally with 2Abz23S29. Moreover, low-dose 2Abz23S29 significantly decreased the level of the interleukin-6 (IL-6), whereas high-dose 2Abz23S29 increased pro-inflammatory cytokines including IL-6, macrophage inflammatory protein/2 (MIP/2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in infected bladders of mice. Besides, the levels of cytokines IL-6 and MIP/2 in infected mice treated with a combination of high-dose 2Abz23S29 and cip were significantly higher than the untreated mice. In contrast, CFT073-infected mice treated with a combination of high-dose 2Abz23S29 and cip showed no changes in cytokines TNF-α and IL-1β levels, indicating that ciprofloxacin may play an anti-inflammatory role. Conclusion: Collectively, apart from the direct antibacterial role of 2Abz23S29, our data illustrated that 2Abz23S29 modulates pro-inflammatory cytokine production of bladder in a dose-dependent manner, which has implications for the development of new anti-infective agents.
机译:介绍:尿道感染(UTI)通常由尿鼠母细胞(UPEC)菌株引起,每年影响全世界的许多人。 UPEC导致膀胱上皮细胞产生促炎细胞因子;然而,已证明UPEC可以抑制先天免疫系统的早期激活。方法:本研究旨在检测不同剂量的截短的α-脱蜡素(人嗜中性粒细胞肽(HNP)-1)模拟2ABZ23S29对小鼠UTI模型的抗菌和免疫调节作用。用低剂量2ABZ23S29(250μg/ mL),高剂量2abz23S29(750μg/ mL),环氟氯嘧汀(CIP)(800μg/ mL),或高剂量2abz23S29PLE CIP处理实验尿鼠母细胞CFT073感染的小鼠。第24小时后感染后。连续两天给出2ABZ23S29和CIP处理。结果:体内结果表明,用2ABZ23S29经过近体经过经过近体经过经过经过经过调节的小鼠的膀胱回收较少的UPEC。此外,低剂量2ABZ23S29显着降低了白细胞介素-6(IL-6)的水平,而高剂量2abz23S29增加了促炎细胞因子,包括IL-6,巨噬细胞炎症蛋白/ 2(MIP / 2),肿瘤坏死因子-α(TNF-α)和小鼠感染膀胱的白细胞介素-1β(IL-1β)。此外,用高剂量2ABZ23S29和CIP组合处理的感染小鼠中细胞因子IL-6和MIP / 2的水平显着高于未处理的小鼠。相反,用高剂量2abz23S29和CIP的组合处理的CFT073感染的小鼠在细胞因子TNF-α和IL-1β水平的情况下没有变化,表明环丙沙星可能发挥抗炎作用。结论:统称,除了2ABZ23S29的直接抗菌作用外,我们的数据显示,2ABZ23S29以剂量依赖的方式调节膀胱的促炎细胞因子产生,这对新的抗感染剂的开发有影响。

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