Ethanol (EtOH) is the most widely abused substance in the United States, and it contributes to well-documented harmful (at high dosages) and beneficial (at low dosages) changes in inflammatory and immune responses. Lipid rafts have been implicated in the regulation and activation of several important receptor complexes in the immune system, including the TLR4 complex. Many questions remain about the precise mechanisms by which rafts regulate the assembly of these receptor complexes. Results summarized in this review indicate that EtOH acts by altering the LPS-induced redistribution of components of the TLR4 complex within the lipid raft and that this is related to changes in actin cytoskeleton rearrangement, receptor clustering, and subsequent signaling. EtOH provides an example of an immunomodulatory drug that acts at least in part by modifying lipid rafts, and it could represent a model to probe the relationships between rafts, receptor complexes, and signaling.

We examined the effects of bacterial lipopolysaccharide and several recombinant human cytokines (tumor necrosis factor alpha and granulocyte-, macrophage-, and granulocyte-macrophage colony-stimulating factors) on the expression of the genes for the phagocyte cytochrome b, an essential component of the superoxide-generating oxidase. In vitro treatment with lipopolysaccharide, tumor necrosis factor alpha, or macrophage- or granulocyte-macrophage colony-stimulating factors increased the levels of transcripts for the cytochrome b heavy chain (gp91phox) 9- to 22-fold and transcripts for the light chain (p22phox) 2- to 5-fold in cultured human monocyte-derived macrophages. The same agents, except for macrophage colony-stimulating factor, induced the expression of the cytochrome b heavy chain gene 2- to 12-fold and light chain gene 2- to 6-fold in human granulocytes. The expression of the cytochrome b heavy and light chain genes was coordinated in both macrophages and neutrophils with regard to stimulus specificity and dose-response pattern. The time course for induction of the two genes was parallel in both cell types for all stimuli. The macrophage response to lipopolysaccharide occurred at least in part at the transcriptional level. These results show that a variety of physiological regulators modulate the coordinated expression of the cytochrome b genes.