Triptolide Inhibits Preformed Fibril-Induced Microglial Activation by Targeting the MicroRNA155-5p/SHIP1 Pathway

Figure 8

T10 inhibited NF-κB activity via miR155-5p/SHIP1 axis. PPFs may bind to the TLR1/2 or TLR4; IKKα/β is therefore activated through IRAK1/TRAF6 signaling. IKKα/β, in turn, phosphorylated IκBα, which results in dissociation of the IκBα form NF-κB. Activated NF-κB is then translocated into nuclei where it binds to specific sequences of DNA, resulting in upregulation of TNFα and IL-1β. T10 could inhibit the expression of miR155-5p, which is capable of negatively regulating SHIP1 expression. Overexpressed SHIP1 mediated by T10, in turn, inhibits activation of IKKα/β through PI3K/Akt signaling, finally resulting in inhibition of NF-κB activity and corresponding repression of TNFα and IL-1β.