TIRAP positively regulates BV2 cells M1 polarization.

Microglia activation, including classical (M1) activation and alternative (M2) activation, plays important roles in the development of several CNS disorders and promotes tissue reconstruction. TLR4 is important for microglia polarization. TIRAP is an intracellular adaptor protein and responsible for the early phase of TLR4 activation. The role of TIRAP in BV2 cells M1 polarization are still unknown. In this study, we showed that TIRAP expression is extremely elevated in LPS/IFN-γ-treated microglia. TIRAP over-expression promoted BV2 microglia M1 polarization by increasing M1-related makers production (iNOS, CD86, IL-6, IL-1β and TNF-α). In contrast, TIRAP knockdown prevented M1-related makers production. Mechanistically, TIRAP could interact with TRAF6 to increase M1-related makers production in TIRAP overexpressed and LPS/IFN-γ-treated BV2 cells. In addition, silence of TIRAP effectively inhibited the activation of the TAK1/IKK/NF-κB signaling pathway and the phosphorylation of Akt and MAPKs which were activated by LPS/IFN-γ stimulation. Thus, our results suggest that TIRAP positively regulate BV2 microglia M1 polarization through TLR4-mediated TAK1/IKK/NF-κB, MAPKs and Akt signaling pathways. This article is protected by copyright. All rights reserved.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}