title: Proinflammatory activation pattern of human umbilical vein endothelial cells induced by IL-1β, TNF-α, and LPS.
abstract: Endothelial cells play a critical role in inflammation by responding to several endogenous and exogenous proinflammatory stimuli. The three most studied factors that provide inflammatory signals to endothelial cells are lipopolysaccharide (LPS), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β; however, their effects on endothelial cells were thoroughly compared at the level of gene expression only. Therefore, our aim was to assess the differences in the signaling pathways, adhesion molecules, and cytokines induced by proinflammatory factors in human umbilical vein endothelial cells (HUVEC). In this study, we demonstrated that signaling of LPS was less effective than that of IL-1β, and was significantly slower than that ofTNF-α and IL-1β, which can be partially explained by the special localization of Toll-like receptor 4 (TLR4). We showed that TLR4 is mainly localized in Golgi apparatus in HUVEC. The proinflammatory capacity of TNF-α was similar to that of IL-1β in inducing NF-κB nuclear translocation, while IL-1β was the strongest activator of MAPK pathways. Moreover, expression of E-selectin, IL-6, and IL-8 was induced most efficiently by IL-1β, while LPS and TNF-α had less effect, whereas we did not find such a difference in ICAM-1 and MCP-1 expression. Due to the higher induction of E-selectin and IL-8, IL-1β might have more important role in neutrophil recruitment than LPS and TNF-α. By above-mentioned parameters we identified a signaling and expression pattern for the three proinflammatory molecules. This pattern illustrates how complex a proinflammatory process can be, and may enable us to predict and compare the pathomechanism of various inflammatory diseases.
authors.affiliation: Third Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Makó
authors.forename: Judit
authors.initials: J
authors.lastname: Czúcz
authors.forename: Zsóka
authors.initials: Z
authors.lastname: Weiszhár
authors.forename: Eszter
authors.initials: E
authors.lastname: Herczenik
authors.forename: János
authors.initials: J
authors.lastname: Matkó
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
authors.forename: László
authors.initials: L
authors.lastname: Cervenak
mesh_terms: D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D010766:Phosphorylation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4