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新型鸡白细胞介素-11的鉴定及其功能特性研究,包括细胞因子产生调节

Identification and functional characterization, including cytokine production modulation, of the novel chicken Interleukin-11.

作者信息

Truong Anh Duc, Hong Yeojin, Rengaraj Deivendran, Lee Janggeun, Lee Kyungbaek, Hong Yeong Ho

机构信息

Department of Animal Science and Technology, Chung-Ang University, Anseong, 17546, Republic of Korea; Department of Biochemistry and Immunology, National Institute of Veterinary Research, 86 Truong Chinh, Dong Da, Hanoi, Viet Nam.

Department of Animal Science and Technology, Chung-Ang University, Anseong, 17546, Republic of Korea.

出版信息

Dev Comp Immunol. 2018 Oct;87:51-63. doi: 10.1016/j.dci.2018.05.017. Epub 2018 May 22.

Abstract

Interleukin (IL)-11 plays an important role in the immune system. However, IL-11 has not yet been characterized in avian species, including chickens. This study is the first to clone and functionally characterize chicken IL-11 (chIL-11). Multiple alignments and phylogenetic tree comparisons of chIL-11 with IL-11 proteins from other species revealed high levels of conservation and a close relationship between chicken and Japanese quail IL-11. Our results demonstrate that chIL-11 was a functional ligand of IL-11RA and IL-6ST in chicken HD11 and OU2 cell lines, as well as activated and regulated JAK-STAT, NF-κB, PI3K/AKT, and MAPK signaling pathways in chicken cell lines. In addition, chIL-11 inhibited nitric oxide production, affected proliferation of both tested cell lines, inhibited Type 1 and 17 T helper (Th) cytokine and IL-26, IL-12, and IL-17A-induced interferon-γ production, and enhanced Th2 cytokine (IL-4 and IL-10) production. Taken together, functional analysis of chIL-11 revealed it bound to IL-11RA and IL-6ST and activated the JAK-STAT, NF-κB, and MAPK signaling pathways, which resulted in modulation of Th1/Th17 and Th2 cytokine production in chicken HD11 and OU2 cell lines. Overall, this indicates chIL-11 has a role in both the innate and adaptive immune system.

摘要

白细胞介素(IL)-11在免疫系统中发挥着重要作用。然而,IL-11在包括鸡在内的禽类物种中尚未得到表征。本研究首次克隆并对鸡白细胞介素-11(chIL-11)进行功能表征。chIL-11与其他物种的IL-11蛋白的多序列比对和系统发育树比较显示,chIL-11具有高度保守性,且鸡和日本鹌鹑的IL-11之间关系密切。我们的结果表明,chIL-11是鸡HD11和OU2细胞系中IL-11RA和IL-6ST的功能性配体,并且在鸡细胞系中激活并调节了JAK-STAT、NF-κB、PI3K/AKT和MAPK信号通路。此外,chIL-11抑制一氧化氮的产生,影响两种受试细胞系的增殖,抑制1型和17型辅助性T(Th)细胞因子以及IL-26、IL-12和IL-17A诱导的干扰素-γ的产生,并增强Th2细胞因子(IL-4和IL-10)的产生。综上所述,chIL-11的功能分析表明它与IL-11RA和IL-6ST结合并激活JAK-STAT、NF-κB和MAPK信号通路,从而导致鸡HD11和OU2细胞系中Th1/Th17和Th2细胞因子产生的调节。总体而言,这表明chIL-11在先天免疫系统和适应性免疫系统中均发挥作用。

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