College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon 24341, Korea.
Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Gangwon 24341, Korea.
Cells. 2021 Jul 2;10(7):1660. doi: 10.3390/cells10071660.
Lipocalin-2 (LCN2), a small secretory glycoprotein, is upregulated by toll-like receptor (TLR) signaling in various cells and tissues. LCN2 inhibits bacterial growth by iron sequestration and regulates the innate immune system. Inflammasome activates the inflammatory caspases leading to pyroptosis and cytokine maturation. This study examined the effects of inflammasome activation on LCN2 secretion in response to TLR signaling. The triggers of NLRP3 inflammasome activation attenuated LCN2 secretion while it induced interleukin-1β in mouse macrophages. In mice, NLRP3 inflammasome activation inhibited TLR-mediated LCN2 secretion. The inhibition of NLRP3 triggers on LCN2 secretion was caused by the inhibited transcription and translation of LCN2. At the same time, no changes in the other cytokines and IκBζ, a well-known transcriptional factor of transcription, were observed. Overall, NLRP3 triggers are a regulator of LCN2 expression suggesting a new linkage of inflammasome activation and LCN2 secretion in the innate immunity.
脂钙蛋白 2（LCN2）是一种小的分泌性糖蛋白，可被各种细胞和组织中的 toll 样受体（TLR）信号上调。LCN2 通过铁螯合抑制细菌生长，并调节先天免疫系统。炎性体激活炎症半胱天冬酶导致细胞焦亡和细胞因子成熟。本研究探讨了炎性体激活对 TLR 信号反应中 LCN2 分泌的影响。NLRP3 炎性体激活的触发因素减弱了 LCN2 的分泌，同时诱导了小鼠巨噬细胞中白细胞介素 1β的产生。在小鼠中，NLRP3 炎性体激活抑制了 TLR 介导的 LCN2 分泌。NLRP3 触发因素对 LCN2 分泌的抑制是由于 LCN2 的转录和翻译受到抑制所致。同时，观察到其他细胞因子和 IκBζ（一种众所周知的转录因子）没有变化。总体而言，NLRP3 触发因素是 LCN2 表达的调节剂，提示炎性体激活和先天免疫中 LCN2 分泌之间存在新的联系。
