Effects of ethanol on NF-kappaB activation, production of myeloid growth factors, and adhesive events in human endothelial cells.
Because neutropenia may aggravate infections in alcoholics, effects of ethanol on the generation of myeloid growth factors by human umbilical vein endothelial cells (HUVECs) and on interactions with neutrophils were examined in vitro. Exposure of HUVECs to ethanol (0.01%-1%) dose-dependently inhibited (by 12%-27%) the release of stem cell factor, granulocyte-macrophage and granulocyte colony-stimulating factors (CSFs), or interleukin (IL)-8, but not of macrophage CSF triggered by lipopolysaccharide (LPS) or IL-1. Ethanol also inhibited the LPS-induced increase in HUVECs to bind neutrophils by 28% (without affecting the expression of intracellular adhesion molecule-1 and E-selectin) and inhibited the translocation of the p65 subunit of NF-kappaB from the cytoplasm to the nucleus by 46%. Thus, exposure of HUVECs to ethanol inhibited the generation of cytokines important for myeloid cell development and reduced the adhesiveness of HUVECs for neutrophils: effects that are possibly linked to the reduced activation of NF-kappaB.
Jonsson
A S
AS
Center for Inflammation and Hematology Research, Departments of Medicine and Hematology, Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden.
Palmblad
J E
JE
D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D019089:Stem Cell Factor / Q000096:biosynthesis; D013926:Thrombopoietin / Q000096:biosynthesis; D014471:Umbilical Veins
D016207:Cytokines; D006133:Growth Substances; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D000431:Ethanol; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin