Fig. 7: Schematic representation of BIG1 in sepsis.
From: BIG1 controls macrophage pro-inflammatory responses through ARF3-mediated PI(4,5)P2 synthesis
BIG1 plays a crucial role in mediating the activation of TLR4-MyD88 signaling pathways through its interaction with ARF3 during the pathological process of sepsis. BIG1 deficiency caused an inhibitory ARF3 activation, which inhibited the activation of PIP5K induced by LPS, resulting in the reduced PIP2 production and the recruitment of TIRAP to the plasma membrane. This caused an inhibitory activation of TLR4-MyD88 signaling pathway, and eventually decreased the production of pro-inflammatory cytokines, and alleviated the inflammatory injury resulted from sepsis.
