further investigation. However, in our experiments, chronic alcohol alone exhibited inhibition of IRAK-M at the mRNA and protein level in monocytes even in the absence of other cell types. Recent studies show that using a human monocytic cell line Mono Mac 6 cells, chronic alcohol increased activation of the TNF-α promoter and its production and this was dependent on activation of the TRIF-IRF3 pathway (47). Whereas chronic alcohol-induced NFκB activation observed in our studies could occur via the MyD88-IRAK-1 pathway, a role for its activation via the TRIF-IRF3-TBK-1 pathway cannot be ruled out.
