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肺部和胸腺中的抗病毒免疫反应:免疫蛋白酶体亚基 LMP2、LMP7 和 MECL-1 在猪中的分子特征和表达分析。

Anti-viral immune response in the lung and thymus: Molecular characterization and expression analysis of immunoproteasome subunits LMP2, LMP7 and MECL-1 in pigs.

机构信息

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.

出版信息

Biochem Biophys Res Commun. 2018 Aug 25;502(4):472-478. doi: 10.1016/j.bbrc.2018.05.190. Epub 2018 Jun 1.

Abstract

Both the lung and the thymus are vital target organ for pathogens including viruses. The immunoproteasome (i-proteasome) enhances antigen presentation for MHC class I molecules to activate CD8+T lymphocyte. These facilitate antiviral adaptive immune response. Our previous study found that, expression of i-proteasome subunits in porcine lung was altered during normal and inflammatory conditions. To date, the expression of i-proteasome subunits in porcine thymus to viruses has not been investigated. In the present study, LMP2, LMP7, and MECL-1 were cloned, identified and their sequences encoded predicted proteins of 216, 275, and 278 amino acids, respectively. Expression of LMP2, LMP7, and MECL-1, in the cytoplasm and nucleus, was markedly altered in the porcine reproductive and respiratory syndrome virus (PRRSV)-infected lung and thymus. And dendritic cells and epithelial cells readily expressed the i-proteasome subunit LMP2 in the thymus of PRRSV-infected pigs compared to that in mock-infected pigs. Additionally, the in vitro stimulation of a PAM cell line with PolyI:C for 12 and 24 h resulted in increased LMP2, LMP7, and MECL-1 expression. These results suggest a central role for these complexes in the activation of an antiviral immune response in pigs. A better understanding of the role of the i-proteasome in different cell types, tissues, and hosts could improve vaccine design and facilitate the development of effective treatment strategies for viral infections.

摘要

肺和胸腺都是病原体(包括病毒)的重要靶器官。免疫蛋白酶体(i-proteasome)增强了 MHC Ⅰ类分子的抗原呈递,从而激活 CD8+T 淋巴细胞。这有助于抗病毒适应性免疫反应。我们之前的研究发现,猪肺中 i-proteasome 亚基的表达在正常和炎症条件下发生改变。迄今为止,尚未研究病毒感染对猪胸腺中 i-proteasome 亚基的表达。在本研究中,克隆、鉴定了 LMP2、LMP7 和 MECL-1,并分别预测其编码的 216、275 和 278 个氨基酸的蛋白质。在猪繁殖与呼吸综合征病毒(PRRSV)感染的肺和胸腺中,LMP2、LMP7 和 MECL-1 在细胞质和细胞核中的表达明显改变。与 mock 感染猪相比,PRRSV 感染猪的胸腺中的树突状细胞和上皮细胞更容易表达 i-proteasome 亚基 LMP2。此外,用 PolyI:C 体外刺激 PAM 细胞系 12 和 24 h 后,LMP2、LMP7 和 MECL-1 的表达增加。这些结果表明这些复合物在猪的抗病毒免疫反应激活中起核心作用。更好地了解 i-proteasome 在不同细胞类型、组织和宿主中的作用,可以改善疫苗设计,并为病毒感染的有效治疗策略的发展提供帮助。

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