Pharmacological modulation of interleukin 1 production by cultured endothelial cells from human umbilical veins.
Solid-phase enzyme immunoassays (with high-turnover acetylcholinesterase as label) for human IL-1 alpha and IL-1 beta were applied to quantify the production of these factors by cultured human umbilical vein endothelial cells (HUVECs). Immunoreactive IL-1s exhibited a typical pattern in HUVECs, under either basal or stimulated conditions: the alpha form was predominant over the beta form and the cell-associated IL-1s measured were more abundant than the material recovered in the supernatants. Bacterial lipopolysaccharide (LPS, 0.5-5 micrograms/ml) significantly increased the basal production of IL-1. Pulses of recombinant IL-1 alpha or -beta or of TNF-alpha followed by a 24 h culture period were also associated with an increased endothelial production of IL-1, with a higher proportion of material secreted in the supernatants as compared with LPS. Other cytokines applied as pulses failed to induce the IL-1s or to modify LPS-induced production of IL-1: they include IL-2, immune interferon, GM-CSF, TGF-beta and EGF. Pharmacological modulators of LPS-induced IL-1 production were identified: glucocorticoids were inhibitors whereas retinoic acid and 1.25-dihydroxy-vitamin D3 had no effects and prostaglandin E2 and IBMX were weak inhibitors. There is no evidence that IL-1 alpha and IL-1 beta are regulated differently in HUVECs, but several significant differences from the monocyte were observed in the regulation of HUVEC IL-1 production.
Unité de recherche Inflammation et Immuno-Rhumatologie, Centre Hospitalier de l'Université Laval, Laurier, Québec, Canada.
P E
PE
Poubelle
J
J
Grassi
P
P
Pradelles
F
F
Marceau
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001685:Biological Factors / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines; D015232:Dinoprostone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine