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. Author manuscript; available in PMC: 2016 Aug 1.
Published in final edited form as: Alcohol. 2015 May 14;49(5):435–452. doi: 10.1016/j.alcohol.2015.04.006

Figure 2.

Figure 2

Evidence supporting a role for Neuroimmune Signaling Cascades in Ethanol Induced Pathology. A simplified schematic of HMGB1, TLR and RAGE signaling cascades that lead to increased transcription of proinflammatory innate immune genes. HMGB1 stimulation of TLRs leads to kinase and/or reactive oxygen species (ROS) activation of nuclear factor kappa B (NF-kB) and activator protein-1 (AP1) the generation increasing transcription of proinflammatory genes. Similarly, activation of the RAGE receptor leads to downstream activation of NF-κB. The production of NF-κB leads to the secretion of proinflammatory gene expression, neuroimmune induction, and cell death. Abbreviations: AP-1: activator protein-1; CD14: Cluster of differentiation 14; ERK: Extracellular signal-regulated kinase; HMGB1: high-mobility group box-1; IKK: inhibitor of nuclear factor kappa-B; JNK: c-Jun N-terminal kinases; LPS: lipopolysaccharide; MyD88: myeloid differentiation primary response gene 88; NADPH oxidase: nicotinamide adenine dinucleotide phosphate-oxidase; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; RAGE: receptor for advanced glycation end products; ROS: reactive oxygen species; Src: Proto-oncogene tyrosine-protein kinase; TIRAP: Toll/Interleukin-1 receptor domain-containing adaptor protein; TLRs: Toll-like receptors.