title: Role of TLR4 in ethanol effects on innate and adaptive immune responses in peritoneal macrophages.
abstract: Toll-like receptors (TLRs) play an important role in the innate immune response and these receptors link innate and adaptive responses. We have reported that ethanol modulates TLR4 receptors by activating or inhibiting its response. However, the role of TLRs in the effects of ethanol on the innate and adaptive responses during acute or chronic treatment is presently unknown. Peritoneal macrophages of wild-type and TLR4-deficient mice treated with acute ethanol (4 g kg(-1), intraperitoneally) or chronic ethanol consumption (5 months) were used. Here we report how acute ethanol dose induces inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, macrophage inflammatory protein 1α (MIP-1α), interferon β1 and IL-12β) and chemokines (monocyte chemoattractant protein -1α and MIP-1α), and upregulates major histocompatibility complexes class I and II (MHC-I and -II), but inhibits the activation of the costimulatory molecules (CD86 and CD40), leading to the suppression of the CD4(+) T-cell proliferation in the macrophages of wild-type mice. Chronic ethanol consumption downregulates the number of F4/80(+) cells expressing MHC-I and -II and decreases CD4(+) T-cell activation in wild-type mice. Interestingly, elimination of TLR4 abolishes the effects of ethanol on the innate and the adaptive inflammatory response induced by both ethanol treatments in macrophages. Taken together, our findings support the role of TLR4 in the effects of ethanol on the immune system, and suggest that alterations in the function of this receptor might modulate the immune response induced by alcohol abuse.
authors.affiliation: Department of Cellular Pathology, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Pascual
authors.forename: Sara
authors.initials: S
authors.lastname: Fernández-Lizarbe
authors.forename: Consuelo
authors.initials: C
authors.lastname: Guerri
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008285:Major Histocompatibility Complex; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000473:pathology; D010587:Phagocytosis / Q000276:immunology; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*
chemical_list: D018925:Chemokines; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D051197:Toll-Like Receptor 4; D000431:Ethanol