Newcastle disease (ND) is an acute, febrile, and highly contagious disease caused by the Newcastle disease virus (NDV), an important pathogen harmful to domestic poultry. Virulent NDV strain infection induces IL-1β expression and along with strong inflammatory response, ultimately results in death. Inhibition or overexpression of S1PR1, an important target for inflammatory disease treatment, regulates IL-1β expression, suggesting that S1PR1 may alter the degree of the inflammatory response induced by NDV infection by regulating pro-inflammatory cytokine expression. However, the molecular mechanism by which S1PR1 regulates IL-1β expression remains unclear. Here, we explore the expression and tissue distribution of S1PR1 after NDV infection and found that S1PR1 expression increased in the lungs, bursa of Fabricius, and DF-1. IL-1β expression induced by NDV was increased following treatment of cells with the S1PR1-specific agonist, SEW2871. In contrast, IL-1β expression induced by NDV was decreased after cells were treated with the S1PR1 inhibitor W146, suggesting that S1PR1 promotes NDV-induced IL-1β expression. Further investigation demonstrated that NDV induced IL-1β expression through p38, JNK/MAPK, and NLRP3/caspase-1 signaling molecules and S1PR1 affected the expression of IL-1β by activating the NLRP3/caspase-1 inflammasome but had no significant effect on p38 and JNK/MAPK. Our study shows that NDV infection promotes S1PR1 expression and induces IL-1β expression through p38, JNK/MAPK, and NLRP3/caspase-1 inflammasomes and that S1PR1 regulates IL-1β expression mainly through the NLRP3/caspase-1 inflammasome.

中文翻译：

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S1PR1 通过 NLRP3/caspase-1 炎性体调节 NDV 诱导的 IL-1β 表达

新城疫（ND）是由对家禽有害的重要病原体新城疫病毒（NDV）引起的一种急性、发热、高度传染性疾病。毒性 NDV 毒株感染诱导 IL-1β 表达并伴随强烈的炎症反应，最终导致死亡。炎症性疾病治疗的重要靶点 S1PR1 的抑制或过表达可调节 IL-1β 表达，这表明 S1PR1 可能通过调节促炎细胞因子表达来改变 NDV 感染诱导的炎症反应程度。然而，S1PR1 调节 IL-1β 表达的分子机制仍不清楚。在这里，我们探索了 NDV 感染后 S1PR1 的表达和组织分布，发现 S1PR1 在肺、法氏囊和 DF-1 中的表达增加。在用 S1PR1 特异性激动剂 SEW2871 处理细胞后，NDV 诱导的 IL-1β 表达增加。相反，在用 S1PR1 抑制剂 W146 处理细胞后，NDV 诱导的 IL-1β 表达降低，表明 S1PR1 促进 NDV 诱导的 IL-1β 表达。进一步研究表明，NDV 通过 p38、JNK/MAPK 和 NLRP3/caspase-1 信号分子诱导 IL-1β 表达，S1PR1 通过激活 NLRP3/caspase-1 炎性体影响 IL-1β 的表达，但对 p38 无显着影响和 JNK/MAPK。我们的研究表明，NDV 感染通过 p38、JNK/MAPK 和 NLRP3/caspase-1 炎性体促进 S1PR1 表达并诱导 IL-1β 表达，并且 S1PR1 主要通过 NLRP3/caspase-1 炎性体调节 IL-1β 表达。