Dyrk2 mediated the release of proinflammatory cytokines in LPS-induced BV2 cells

NF-kappa B pathway and p38MAPK (p38mitogen-activated protein kinase) pathway have been shown to play a key role in neuroinflammation, however, the phosphorylation modification is an important process that affects the activation of above pathways. Dual-specificity tyrosine-phosphorylation-regulated kinase 2(Dyrk2), as a phosphokinase that can phosphorylate signal molecules, has been demonstrated to regulate Type I Interferon(TIF) by promoting ser527 phosphorylation of TBK1. Therefore, to investigate the role of Dyrk2 in neuroinflammation, we analyzed the effect of Dyrk2 on LPS-induced the activation of microglia. Here, we found Dyrk2 expressed in BV2 cells, and LPS induced different expression trend of Dyrk2 in the cytoplasm and nucleus. In addition, we revealed that Dyrk2 interacted with Akt, p38MAPK and NF-kappa B subunit p65, however, in the nucleus of BV2 cells, Dyrk2 selectively interacted with p38MAPK instead of with p65. Although the overexpression of Dyrk2 increased the expression level of phospho-p65, phospho-Akt and phospho-p38MAPK in LPS-stimulated BV2 cells, less TNF-alpha and IL-1 beta were detected. Probably, the inhibitory effect of Dyrk2 on the release of TNF-alpha and IL-1 beta was associated with the induction of phospho-Akt. In conclusion, these data suggested Dyrk2 involved in regulating LPS-induced the release of proinflammatory cytokines through its phosphokinase function. (C) 2017 Elsevier B.V. All rights reserved.