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重组丝虫蛋白 rWbL2 的免疫调节潜力及其在实验性溃疡性结肠炎小鼠模型中的治疗意义。

Immunomodulatory potential of recombinant filarial protein, rWbL2, and its therapeutic implication in experimental ulcerative colitis in mouse.

机构信息

a Department of Biochemistry and JB Tropical Disease Research Center , Mahatma Gandhi Institute of Medical Sciences , Sevagram , Maharashtra , India.

b Department of Anatomy , Mahatma Gandhi Institute of Medical Sciences , Sevagram , Maharashtra , India.

出版信息

Immunopharmacol Immunotoxicol. 2018 Dec;40(6):483-490. doi: 10.1080/08923973.2018.1431925. Epub 2018 Feb 7.

Abstract

OBJECTIVE

Immunomodulation by helminth proteins has potential therapeutic implications in inflammatory bowel disease. In the present study, we have explored the therapeutic effect of a RAL family protein of filarial parasite Wuchereria bancrofti i.e., rWbL2 protein against DSS induced colitis in a mouse model.

MATERIALS AND METHODS

Anti-inflammatory activity of rWbL2 on mice peritoneal exudate cells was analyzed under in vitro condition. The colitis mice were treated intraperitoneally (i.p.) with rWbL2 in increasing doses (10 µg, 25 µg, and 50 µg) on days 4, 5, and 6. Disease severity was assessed by disease activity index (DAI), macroscopic and histopathological scores, and enzyme myeloperoxidase activity (MPO) in the colon. The response of the cultured splenocytes from treated mice to Con-A stimulation, in terms of ELISA-based assessment of the protein followed by the assessment of mRNA expression of cytokines, was measured by real-time PCR analysis.

RESULT

rWbL2 protein showed anti-inflammatory activity in vitro. Treatment with rWbL2 (at 25 µg/dose) effectively attenuated disease severity by reducing weight loss, DAI, mucosal edema, colon damage, and MPO activity. This therapeutic effect was found to be associated with increased release of anti-inflammatory cytokine IL-10 and decreased release of pro-inflammatory cytokine IFN-γ and TNF-α by the splenocytes of treated mice followed by stimulation with Con-A.

CONCLUSIONS

These results provide evidence of the strong immunomodulatory potential of rWbL2 protein implicating its therapeutic application against ulcerative colitis.

摘要

目的

寄生虫蛋白的免疫调节作用在炎症性肠病中有潜在的治疗意义。在本研究中,我们探索了丝虫寄生虫班氏吴策线虫的 RAL 家族蛋白,即 rWbL2 蛋白,对 DSS 诱导的小鼠结肠炎模型的治疗作用。

材料和方法

在体外条件下分析 rWbL2 对小鼠腹腔渗出细胞的抗炎活性。在第 4、5 和 6 天,用 rWbL2 以递增剂量(10μg、25μg 和 50μg)腹腔内(i.p.)治疗结肠炎小鼠。通过疾病活动指数(DAI)、宏观和组织病理学评分以及结肠中髓过氧化物酶(MPO)活性来评估疾病严重程度。通过 ELISA 评估培养的脾细胞对 Con-A 刺激的反应,然后通过实时 PCR 分析评估细胞因子的 mRNA 表达,来测量来自治疗小鼠的脾细胞的反应。

结果

rWbL2 蛋白在体外显示出抗炎活性。用 rWbL2(25μg/剂量)治疗可有效减轻疾病严重程度,减少体重减轻、DAI、粘膜水肿、结肠损伤和 MPO 活性。这种治疗效果与治疗小鼠脾细胞释放更多抗炎细胞因子 IL-10 和更少的促炎细胞因子 IFN-γ 和 TNF-α有关,随后用 Con-A 刺激。

结论

这些结果提供了 rWbL2 蛋白具有强大免疫调节潜力的证据,暗示其在治疗溃疡性结肠炎方面的应用。

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