JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.9 P.782-790

Aeromonas sobria regulates proinflammatory immune response in mouse macrophages via activating the MAPK, AKT, and NF-κB pathways

Author(s): Wei ZHANG, Bello Babatunde KAZEEM, Haitao YANG, Gang LIU, Guanglu WANG, Zhixing LI, Tao GUO, Panpan ZHAO, Jingquan DONG
Affiliation(s): Key Jiangsu Institute of Marine Resources Development, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang 222005, China; more
Corresponding email(s): zhaopp19@mails.jlu.edu.cn, 2018000029@jou.edu.cn
Key Words: Aeromonas sobria, MAPK, NF-?B p65, Proinflammatory cytokines, Immune response

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Abstract: aeromonas sobria, a Gram-negative bacterium that can colonize both humans and animals, is found in a variety of environments, including water, seafood, meat, and vegetables (Cahill, 1990; Galindo et al., 2004; Song et al., 2019). Aeromonas spp. are conditionally pathogenic bacteria in aquaculture, which can rapidly proliferate, causing disease and even death in fish, especially when the environment is degraded (Neamat-Allah et al., 2020, 2021a, 2021b). In developing countries, Aeromonas spp. have been associated with a wide spectrum of infections in humans, including gastroenteritis, wound infections, septicemia, and lung infections (San Joaquin and Pickett, 1988; Wang et al., 2009; Su et al., 2013). Infections caused by Aeromonas spp. are usually more severe in immunocompromised individuals (Miyamoto et al., 2017). The presence of a plasmid encoding a β‍-lactamase in A. sobria that confers resistance to β-lactam antibiotics poses a huge challenge to the treatment of diseases caused by this microorganism (Lim and Hong, 2020). Consequently, an in-depth understanding of the interaction between A. sobria and its hosts is urgently required to enable the development of effective strategies for the treatment of A. sobria infections.

MAPK、AKT和NF-κB信号通路在温和气单胞菌诱导宿主细胞炎性应答中的作用及分子机制研究

目的：以利用小鼠原代腹腔巨噬细胞建立了一种温和气单胞菌体外感染模型，探究MAPK、AKT和NF-κB信号通路在温和气单胞菌诱导宿主细胞炎性应答中的作用及相关的分子机制，为防治温和气单胞菌造成的感染提供新的治疗靶点。
创新点：首次探究了丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）、蛋白激酶B（protein kinase B，AKT）和核因子κB（nuclear factor kappa B，NF-κB）信号通路在温和气单胞菌诱导宿主细胞炎性应答中的作用及相关的分子机制，并分别从正反向进行了研究，围绕NF-κB、MAPK、磷酯酰肌醇-3-激酶（phosphatidylinositol 3 kinase，PI3K）/AKT等与炎症反应密切相关的信号通路，探索温和气单胞菌调控宿主细胞免疫应答的作用机制，为防治温和气单胞菌感染的治疗提供新的靶点。
方法：本研究利用小鼠原代腹腔巨噬细胞建立了一种温和气单胞菌体外感染模型，通过测定感染细胞培养上清中的炎性细胞因子分泌水平，初步确定其可引起小鼠原代腹腔巨噬细胞产生炎性应答。应用荧光定量PCR、蛋白质免疫印迹、阻断实验、酶联免疫吸附试验和免疫荧光等技术，围绕NF-κB、MAPK、PI3K/AKT等与炎症反应密切相关的信号通路，探索温和气单胞菌调控宿主细胞免疫应答的作用机制，为防治温和气单胞菌感染的治疗提供新的靶点。
结论：温和气单胞菌体外刺激小鼠腹腔巨噬细胞可以引起多种炎性细胞因子分泌水平的升高，如白细胞介素1β（interleukin-1β，IL-1β）、白细胞介素6（interleukin-6，IL-6）、白细胞介素12（interleukin-12，IL-12）和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）。同时温和气单胞菌可以通过p38MAPK、c-Jun氨基末端激酶（c-Jun N-terminal kinase，JNK）/MAPK及NF-κB信号通路调节小鼠腹腔巨噬细胞促炎性因子的转录和表达，并通过AKT信号通路负调节促炎性因子的转录和表达等。因此，p38MAPK、JNK/MAPK和NF-κB信号通路均可作为潜在的药物干预靶点治疗温和气单胞菌引起的各类炎症感染。

关键词：温和气单胞菌；免疫应答；丝裂原活化蛋白激酶（MAPK）；蛋白激酶B（AKT）；核因子κB（NF-κB）

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MAPK、AKT和NF-κB信号通路在温和气单胞菌诱导宿主细胞炎性应答中的作用及分子机制研究

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