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Matrine inhibits IL-1β secretion in primary porcine alveolar macrophages through the MyD88/NF-κB pathway and NLRP3 inflammasome.
Veterinary Research ( IF 3.7 ) Pub Date : 2019-07-12 , DOI: 10.1186/s13567-019-0671-x
Panpan Sun 1, 2 , Na Sun 1 , Wei Yin 1 , Yaogui Sun 1 , Kuohai Fan 3 , Jianhua Guo 4 , Ajab Khan 1 , Yongming He 2 , Hongquan Li 1
Affiliation  

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-κB 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-1β mechanism of matrine, as IL-1β is a major inflammatory cytokine, in porcine alveolar macrophages (PAMs) stimulated with 4 μg PRRSV 5'-untranslated region (UTR) RNA and 1 μg/mL LPS. After 5'UTR RNA and LPS co-stimulation of PAMs for 12 h, the expression of IL-1β, IL-6, IL-8 and TNF-α was significantly increased. The results also showed that co-stimulation induced the expression of MyD88, and activated the NF-κB signalling pathway and NLRP3 inflammasome. Furthermore, matrine treatment downregulated MyD88, NLRP3 and caspase-1 expression, inhibited ASC speck formation, suppressed IκBα phosphorylation, and interfered with the translocation of NF-κB 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-κB and the NLRP3 inflammasome. These findings lay the foundation for the exploration of the clinical application of matrine in PRRSV disease.

中文翻译:

苦参碱通过MyD88 /NF-κB途径和NLRP3炎性小体抑制猪肺泡巨噬细胞中IL-1β的分泌。

我们以前的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,并且还与NF-κB信号通路相关。这些结果表明苦参碱具有抗病毒和抗炎作用。但是,苦参碱的具体抗炎机制仍不清楚。在这项研究中,我们研究了苦参碱的抗IL-1β机制,因为IL-1β是主要的炎症细胞因子,在猪肺泡巨噬细胞(PAM)中受4μgPRRSV 5'-非翻译区(UTR)RNA和1μg刺激/ mL LPS。5'UTR RNA和LPS共刺激PAMs 12 h后,IL-1β,IL-6,IL-8和TNF-α的表达明显增加。结果还表明,共同刺激诱导了MyD88的表达,并激活了NF-κB信号通路和NLRP3炎性小体。此外,苦参碱处理下调了MyD88,NLRP3和caspase-1的表达,抑制了ASC斑点的形成,抑制了IκBα磷酸化,并干扰了NF-κB从细胞质到细胞核的转运。这些结果表明苦参碱在与PRRSV 5'UTR RNA和LPS共同刺激的PAM中起重要作用,因为它对NF-κB和NLRP3炎性小体有影响。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。这些结果表明苦参碱在与PRRSV 5'UTR RNA和LPS共同刺激的PAM中起重要作用,因为它对NF-κB和NLRP3炎性小体有影响。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。这些结果表明苦参碱在与PRRSV 5'UTR RNA和LPS共同刺激的PAM中起重要作用,因为它对NF-κB和NLRP3炎性小体有影响。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。
更新日期:2019-07-12
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