Alcohol has a known proinflammatory effect in multiple organs including the brain (Crews & Vetreno, 2016; J. Mayfield, Ferguson, & Harris, 2013; McClintick et al., 2013) and lymphoblastoid cells (McClintick et al., 2014; McClintick et al., 2019). A few pathways and upstream regulators related to inflammation were increased in the CIE cells, including the key regulators NFκB and cytokines C5, CCL5 and IL11. LTB4R, a receptor for the proinflammatory leukotriene LTB4, had a large increase in expression. Although no Toll-like receptors (TLRs) were detectably expressed in these cells, genes downstream of TLR4 were affected, possibly via effects of related activators such as C5 and NFκB. Both WNT5A and its receptor FZD5 increased in expression; this combination regulates inflammatory responses, linking innate and adaptive immune responses (Blumenthal et al., 2006). The pair can also activate the Wnt5a/JNK pathway which is important in neural differentiation from stem cells (Jang, Park, & Jeong, 2015). The significant FUMA gene sets include 42 sets from Immunologic signatures (Supplementary Table S5).
