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Toll-like receptor-4 (TLR-4) signaling via MyD-88-dependent pathways. Chronic ethanol exposure increases lipopolysaccharide (LPS) in the circulation, and initiates a signaling cascade via TLR-4 on the surface of Kupffer cells. This signaling pathway activates mitogen-activated protein kinases (MAPKs), p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases 1 and 2 (ERK1/2), resulting in increased tumor necrosis factor (TNF)-α expression and stability.
