Porcine Circovirus Type 2 Induces Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR) Downregulation to Promote Interleukin-1β Upregulation in Porcine Alveolar Macrophage
Porcine Circovirus Type 2 Induces Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR) Downregulation to Promote Interleukin-1β Upregulation in Porcine Alveolar Macrophage
复制标题
猪圆环病毒 2 型诱导单一免疫球蛋白白细胞介素 1 相关受体 (SIGIRR) 下调，以促进猪肺泡巨噬细胞中白细胞介素 1β 上调
DOI：
10.3390/v11111021
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发表时间：
2019-11-01
期刊：
影响因子：
4.7
通讯作者：
Cai, Jianping
中科院分区：
文献类型：
--
作者：
Yang, Shunli;Liu, Baohong;Cai, Jianping
受猪圆环病毒 2 型 (PCV2) 影响的猪的多系统炎症表明炎症细胞因子的表达紊乱。然而，PCV2诱导的炎症细胞因子的表达谱及其调节机制仍知之甚少。在本研究中，通过 RT2 ProfilerTM PCR 阵列分析体外分析了 PCV2 感染后猪肺泡巨噬细胞 (PAM) 中的炎症细胞因子和受体。研究了白细胞介素1β（IL-1β）表达的调节机制。结果显示，PCV2 感染后不同阶段的 PAM 中 84 种炎症细胞因子和受体中有 49 种存在差异表达（p < 0.05，绝对倍数变化≥2）。此外，单一免疫球蛋白白细胞介素-1相关受体（SIGIRR）的过度表达或通过其抑制剂阻断NF-κB激活显着减少了IL-1β的分泌。这一发现表明 PCV2 诱导的 IL-1β 过度表达与 SIGIRR 的下调和 NF-κB 的激活有关。此外，SIGIRR 敲除的 PAM 细胞系中 NF-κB 的过度活性表明 SIGIRR 通过抑制 NF-κB 的激活来负向调节 IL-1β 的产生。总体而言，PCV2 诱导的 SIGIRR 下调诱导 NF-κB 激活是增强 PAM 中 IL-1β 产生的关键过程。这项研究可能有助于深入了解猪 PCV2 感染后发生的潜在炎症反应。
Multisystemic inflammation in pigs affected by porcine circovirus type 2 (PCV2) indicates the disordered expression of inflammatory cytokines. However, the PCV2-induced expression profile of inflammation cytokines and its regulating mechanism remain poorly understood. In this study, inflammatory cytokines and receptors in porcine alveolar macrophages (PAMs) after PCV2 infection were profiled in vitro by an RT2 ProfilerTM PCR array assay. The regulatory mechanism of interleukin-1β (IL-1β) expression was investigated. Results showed that 49 of 84 inflammation cytokines and receptors were differentially expressed (p < 0.05, absolute fold change ≥2) in PAMs at different stages post-PCV2 infection. Moreover, the overexpression of single-immunoglobulin interleukin-1 related receptor (SIGIRR) or the blocking of NF-κB activation by its inhibitor markedly decreased IL-1β secretion. This finding suggested that PCV2-induced overexpression of IL-1β was associated with the downregulation of SIGIRR and the activation of NF-κB. Furthermore, the excessive activity of NF-κB in SIGIRR-knockout PAMs cell line, indicating that SIGIRR negatively regulated IL-1β production by inhibiting the activation of NF-κB. Overall, PCV2-induced downregulation of SIGIRR induction of NF-κB activation is a critical process in enhancing IL-1β production in PAMs. This study may provide insights into the underlying inflammatory response that occurs in pigs following PCV2 infection.