title: The endothelium secretes interleukin-6 (IL-6) and induces IL-6 and aldosterone generation by adrenocortical cells.
abstract: Endothelial cells have been shown to induce adrenal steroidogenesis and to enhance aldosterone secretion via angiotensin II and endothelin 1-independent mechanisms. It has been demonstrated that endothelial cells and adrenocortical cells are capable of producing interleukin-6 (IL-6) and IL-6 is a factor known to stimulate adrenal cortisol secretion. We therefore asked whether endothelial cells have an effect on adrenal IL-6 generation and whether IL-6 mediates biosynthesis of aldosterone as is observed after exposure of adrenocortical cells to endothelial cell-conditioned medium (ECCM). Cells from the adrenocortical cancer cell line NCI-H295R were incubated with ECCM produced from human umbilical vein endothelial cells at increasing concentrations. As detected by an enzyme-linked immunosorbent assay, pure ECCM significantly increased IL-6 protein secretion by cultured adrenocortical cells in a dose-dependent fashion, to a 18.0+/-2.0 pg/mL (mean+/-SEM). This was paralleled by an enhanced IL-6 promoter activity as determined with the transfection of an IL-6-promoter-luciferase reporter gene construct. Pure ECCM also induced aldosterone secretion by adrenocortical cells more than three times that of controls with serum-free medium. ECCM PER SE contains significant amounts of IL-6 protein. However, blockade of IL-6 signal transduction did not interfere with aldosterone synthesis. These data suggest that endothelial cells secrete IL-6 and that endothelial cell-derived factors regulate adrenal IL-6 synthesis which does not alter adrenal aldosterone secretion. Our findings support the hypothesis that the endothelium and the adrenal gland may play a role in the development of some forms of hypertension and - more speculative - inflammation.
authors.affiliation: Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Germany. Holger.Willenberg@uni-duesseldorf.de
authors.forename: H S
authors.initials: HS
authors.lastname: Willenberg
authors.forename: I
authors.initials: I
authors.lastname: Ansurudeen
authors.forename: K
authors.initials: K
authors.lastname: Schebesta
authors.forename: M
authors.initials: M
authors.lastname: Haase
authors.forename: B
authors.initials: B
authors.lastname: Wess
authors.forename: S
authors.initials: S
authors.lastname: Schinner
authors.forename: A
authors.initials: A
authors.lastname: Raffel
authors.forename: M
authors.initials: M
authors.lastname: Schott
authors.forename: W A
authors.initials: WA
authors.lastname: Scherbaum
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism*; D019899:Paracrine Communication / Q000502:physiology; D014162:Transfection
chemical_list: D017077:Culture Media, Conditioned; D015850:Interleukin-6; D000450:Aldosterone