a dose-dependent manner (Zhang, Bagby et al. 2001). This inhibitory effect on NFκB activity is partly due to the increased proteolytic degradation of IκBα kinase (IKK) and consequent decreased phosphorylation of the NFκB p65 subunit (Mandrekar, Jeliazkova et al. 2007). Additional studies also showed that exposure of RAW 264.7 macrophages and human peripheral blood monocytes to 25mM of ethanol for as little as 60 minutes results in the activation of the heat shock transcription factor-1 (HSF-1), which in turn induces heat shock protein hsp70 expression (Mandrekar, Catalano et al. 2008). Hsp70 binds the NFκB subunit p50 and decreases its nuclear translocation while HSF-1 binds to the TNF-α promoter region resulting in negative regulation of TLR4 signaling (Mandrekar, Catalano et al. 2008, Muralidharan, Ambade et al. 2014). Finally, in vitro exposure of human peripheral blood monocytes to 25mM ethanol for 6 hours also inhibited TLR8-induced production of the pro-inflammatory cytokine TNF-α and increased production of the antiinflammatory cytokine IL-10 (Pang, Bala et al. 2011).
