Matrine inhibits IL-1β secretion in primary porcine alveolar macrophages through the MyD88/NF-κB pathway and NLRP3 inflammasome
Matrine inhibits IL-1β secretion in primary porcine alveolar macrophages through the MyD88/NF-κB pathway and NLRP3 inflammasome
复制标题
苦参碱通过 MyD88/NF-kappa B 通路和 NLRP3 炎性体抑制原代猪肺泡巨噬细胞中 IL-1 β 的分泌
DOI：
10.1186/s13567-019-0671-x
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发表时间：
2019-07-12
影响因子：
4.4
通讯作者：
Li, Hongquan
中科院分区：
文献类型：
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作者：
Sun, Panpan;Sun, Na;Li, Hongquan
我们的前期研究表明，苦参碱直接作用于猪繁殖与呼吸综合征病毒（PRRSV）的复制过程。苦参碱抑制病毒复制，也与nf - κ B信号通路有关。提示苦参碱具有抗病毒和抗炎作用。然而，苦参碱的具体抗炎机制尚不清楚。在这项研究中，我们研究了苦参碱抗IL-1 β的机制，因为IL-1 β是一种主要的炎症细胞因子，在4 μ g PRRSV 5 '-未翻译区（UTR） RNA和1 μ g/mL LPS刺激的猪肺泡巨噬细胞（PAMs）中。5 ' UTR RNA与LPS共同刺激PAMs 12h后，IL-1 β、IL-6、IL-8、tnf - α的表达显著升高。结果还显示，共刺激诱导了MyD88的表达，激活了nf - κ B信号通路和NLRP3炎性体。此外，苦参碱处理下调MyD88、NLRP3和caspase-1的表达，抑制ASC斑点形成，抑制I κ B α磷酸化，干扰nf - κ B从细胞质向细胞核的易位。这些结果表明，苦参碱通过对nf - κ B和NLRP3炎症小体的影响，在PRRSV 5 ' UTR RNA和LPS共同刺激的pam中发挥了重要作用。这些发现为探索苦参碱在PRRSV疾病中的临床应用奠定了基础。
Our previous studies demonstrated that matrine directly acts on the replication process of porcine reproductive and respiratory syndrome virus (PRRSV). Matrine inhibits viral replication and is also associated with the NF-kappa B signalling pathway. These results suggest that matrine has antiviral and anti-inflammatory effects. However, the specific anti-inflammatory mechanism of matrine is still unclear. In this study, we investigated the anti-IL-1 beta mechanism of matrine, as IL-1 beta is a major inflammatory cytokine, in porcine alveolar macrophages (PAMs) stimulated with 4 mu g PRRSV 5 '-untranslated region (UTR) RNA and 1 mu g/mL LPS. After 5 ' UTR RNA and LPS co-stimulation of PAMs for 12h, the expression of IL-1 beta, IL-6, IL-8 and TNF-alpha was significantly increased. The results also showed that co-stimulation induced the expression of MyD88, and activated the NF-kappa B signalling pathway and NLRP3 inflammasome. Furthermore, matrine treatment downregulated MyD88, NLRP3 and caspase-1 expression, inhibited ASC speck formation, suppressed I kappa B alpha phosphorylation, and interfered with the translocation of NF-kappa B from the cytoplasm to the nucleus. These results suggest that matrine plays an important role in PAMs co-stimulated with PRRSV 5 ' UTR RNA and LPS via its effect on NF-kappa B and the NLRP3 inflammasome. These findings lay the foundation for the exploration of the clinical application of matrine in PRRSV disease.