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分泌白细胞介素-17A细胞因子的重组菌株的抗肿瘤作用

Anti-tumoral Effects of Recombinant Strain Secreting IL-17A Cytokine.

作者信息

Jacouton Elsa, Torres Maravilla Edgar, Boucard Anne-Sophie, Pouderous Nicolas, Pessoa Vilela Ana Paula, Naas Isabelle, Chain Florian, Azevedo Vasco, Langella Philippe, Bermúdez-Humarán Luis G

机构信息

Micalis Institute, AgroParisTech, INRA, Université Paris-Saclay, Jouy-en-Josas, France.

Instituto de Ciências Biológicas, Federal University of Minas Gerais, Belo Horizonte, Brazil.

出版信息

Front Microbiol. 2019 Jan 23;9:3355. doi: 10.3389/fmicb.2018.03355. eCollection 2018.

Abstract

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine produced by T cells that participates and contributes in host defense and autoimmune disease. We have recently reported antitumor properties of the probiotic strain of BL23 in mice and T cells was shown to play an important role in this beneficial effect. In order to better understand the role of IL-17A in cancer, we constructed a recombinant strain of producing this cytokine and we determined its biological activity in: (i) a bioassay test for the induction of IL-6 production by murine fibroblasts 3T3 L1 cells line and (ii) in a mouse allograft model of human papilloma virus (HPV)-induced cancer. Our data show that recombinant produces and efficiently secretes biologically active IL-17A cytokine. Interestingly, ∼26% of mice intranasally treated with -IL-17A and challenged with TC-1 cells remained tumor free over the experiment, in contrast to control mice treated with the wild type strain of which developed 100% of aggressive tumors. In addition, the median size of the ∼74% tumor-bearing mice treated with recombinant -IL-17A, was significantly lower than mice treated with -wt. Altogether, our results demonstrate that intranasal administration with secreting IL-17A results in a partial protection against TC-1-induced tumors in mice, confirming antitumor effects of this cytokine in our cancer model.

摘要

白细胞介素-17A(IL-17A)是一种由T细胞产生的促炎细胞因子,参与宿主防御和自身免疫性疾病并发挥作用。我们最近报道了益生菌菌株BL23在小鼠体内的抗肿瘤特性,并且发现T细胞在这种有益作用中发挥重要作用。为了更好地理解IL-17A在癌症中的作用,我们构建了一种产生这种细胞因子的重组菌株,并在以下方面确定了其生物学活性:(i)通过小鼠成纤维细胞3T3 L1细胞系诱导IL-6产生的生物测定试验,以及(ii)在人乳头瘤病毒(HPV)诱导的癌症的小鼠同种异体移植模型中。我们的数据表明,重组菌株产生并有效分泌具有生物活性的IL-17A细胞因子。有趣的是,在实验过程中,约26%经鼻内给予-IL-17A并接种TC-1细胞的小鼠没有发生肿瘤,相比之下,用野生型菌株处理的对照小鼠100%发生侵袭性肿瘤。此外,用重组-IL-17A处理的约74%荷瘤小鼠的肿瘤中位大小明显低于用-wt处理的小鼠。总之,我们的结果表明,经鼻内给予分泌IL-17A的菌株可使小鼠对TC-1诱导的肿瘤产生部分保护作用,证实了这种细胞因子在我们的癌症模型中的抗肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9338/6351453/01d894831f77/fmicb-09-03355-g001.jpg

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