Porcine Circovirus Type 2 Induces Single Immunoglobulin Interleukin-1 Related Receptor (SIGIRR) Downregulation to Promote Interleukin-1β Upregulation in Porcine Alveolar Macrophage

猪圆环病毒 2 型诱导单个免疫球蛋白白细胞介素 1 相关受体 (SIGIRR) 下调,促进猪肺泡巨噬细胞中白细胞介素 1β 上调

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作者:Shunli Yang, Baohong Liu, Shuanghui Yin, Youjun Shang, Xinming Zhang, Muhammad Umar Zafar Khan, Xiangtao Liu, Jianping Cai

Abstract

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.

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