Department of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun, China.
Signature Research Program in Emerging Infectious Diseases, Duke - National University of Singapore (NUS) Graduate Medical School, Singapore, Singapore.
Front Immunol. 2023 Jan 16;14:1119473. doi: 10.3389/fimmu.2023.1119473. eCollection 2023.
Influenza A virus (IAV) infection leads to severe inflammation, and while epithelial-driven inflammatory responses occur activation of NF-κB, the factors that modulate inflammation, particularly the negative regulators are less well-defined. In this study we show that A20 is a crucial molecular switch that dampens IAV-induced inflammatory responses. Chronic exposure to low-dose LPS environment can restrict this excessive inflammation. The mechanisms that this environment provides to suppress inflammation remain elusive. Here, our evidences show that chronic exposure to low-dose LPS suppressed IAV infection or LPS stimulation-induced inflammation and . Chronic low-dose LPS environment increases A20 expression, which in turn positively regulates PPAR-α and -γ, thus dampens the NF-κB signaling pathway and NLRP3 inflammasome activation. Knockout of A20 abolished the inhibitory effect on inflammation. Thus, A20 and its induced PPAR-α and -γ play a key role in suppressing excessive inflammatory responses in the chronic low-dose LPS environment.
甲型流感病毒（IAV）感染会导致严重的炎症，而当上皮细胞驱动的炎症反应发生时，NF-κB 会被激活，但是调节炎症的因素，特别是负调控因子，还不太明确。在这项研究中，我们表明 A20 是一个关键的分子开关，可以抑制 IAV 诱导的炎症反应。慢性暴露于低剂量 LPS 环境可以限制这种过度的炎症。这种环境提供抑制炎症的机制仍不清楚。在这里，我们的证据表明，慢性低剂量 LPS 暴露抑制了 IAV 感染或 LPS 刺激诱导的炎症。慢性低剂量 LPS 环境增加了 A20 的表达，这反过来又正向调节了 PPAR-α 和 -γ，从而抑制了 NF-κB 信号通路和 NLRP3 炎性体的激活。A20 的敲除消除了对炎症的抑制作用。因此，A20 及其诱导的 PPAR-α 和 -γ 在慢性低剂量 LPS 环境中抑制过度炎症反应中发挥关键作用。
