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Ts19 片段 II 毒素生物活性的扩展:对白细胞介素-17 产生的见解

Expanding biological activities of Ts19 Frag-II toxin: Insights into IL-17 production.

作者信息

Cerni Felipe Augusto, Pucca Manuela Berto, Zoccal Karina Furlani, Frantz Fabiani Gai, Faccioli Lucia Helena, Arantes Eliane Candiani

机构信息

Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Health Sciences Center, Medical School, Federal University of Roraima, Boa Vista, RR, Brazil.

出版信息

Toxicon. 2017 Aug;134:18-25. doi: 10.1016/j.toxicon.2017.05.013. Epub 2017 May 18.

DOI:10.1016/j.toxicon.2017.05.013
PMID:28528178
Abstract

Tityus serrulatus (Ts) venom is composed of a mixture of toxins presenting diverse biological functions. However, although this venom has been studied over the past three decades, omics analysis revealed that most of its toxins are not identified or their biological activities are unknown. Ts19 Frag-II is included in this group, which function is still uncertain. This study aimed to expand the biological activities of Ts19 Frag-II through in vivo investigation. Our results demonstrates that mice challenged with Ts19 Frag-II presented biochemical alterations, increasing serum levels of urea, ALT and β-globulin, besides decreasing γ-globulins. Moreover, this toxin was also able to induce immunological alterations, increasing NO, IL-6, TNF-α and IL-17, being considered a proinflammatory toxin. The increase of IL-17 was unprecedented regarding Ts toxins and could be a result of the overall produced-effect of cells of innate immunity cells (neutrophils, monocytes, natural killers and lymphoid tissue inducers - LTis) as well as of adaptive immunity (Th17 cells). This study expanded the biological activities of Ts19 Frag-II, suggesting that this toxin could be contributing to the Ts envenoming through alterations of biochemical parameters as well as triggering the inflammatory response.

摘要

锯齿脂鲤(Tityus serrulatus, Ts)毒液由具有多种生物学功能的毒素混合物组成。然而,尽管在过去三十年中对这种毒液进行了研究,但组学分析表明,其大多数毒素尚未被鉴定出来,或者其生物学活性未知。Ts19 Frag-II就属于这一类,其功能仍然不确定。本研究旨在通过体内研究扩展Ts19 Frag-II的生物学活性。我们的结果表明,用Ts19 Frag-II攻击的小鼠出现了生化改变,除了γ-球蛋白降低外,血清尿素、谷丙转氨酶(ALT)和β-球蛋白水平升高。此外,这种毒素还能够诱导免疫改变,增加一氧化氮(NO)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和白细胞介素-17(IL-17),被认为是一种促炎毒素。就Ts毒素而言,IL-17的增加是前所未有的,这可能是先天免疫细胞(中性粒细胞、单核细胞、自然杀伤细胞和淋巴组织诱导细胞-LTis)以及适应性免疫(Th17细胞)产生的总体效应的结果。本研究扩展了Ts19 Frag-II的生物学活性,表明这种毒素可能通过改变生化参数以及引发炎症反应,从而导致Ts中毒。

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