Fig. 10

The interaction among MCP-1/CCR2 signaling, TLR4, and GSK3β in ethanol-induced neuroinflammation. EtOH may stimulate TLR4 and possibly CCR2, and activate the downstream effectors, such as TRIF and MyD88. Active TLR4 may also activate GSK3β which may further stimulate TLR4 pathway. As a result, the activation of TRIF, MyD88, and GSK3β stimulates transcription factors which upregulate the expression of proinflammatory cytokines and chemokines (e.g., TNF-α, IL6, and MCP-1). The released MCP-1 interacts with CCR2 and further activates TLR4 and GSK3β; the positive feedback loop intensifies the neuroinflammation that is toxic to neurons in the developing CNS