Modulation of Secretion of Interleukin-6 in Brain-Derived Microvascular Endothelial Cells

Vascular permeability is tightly controlled, in particular in the cerebral microvasculature, thus factors able to modulate permeability are of physiological importance. Interleukin-6 (IL-6) can be released by many cell types including mononuclear phagocytes, fibroblasts and endothelial cells of various origins, and is involved in a variety of cellular responses, including modulation of vascular permeability. IL-6 is synthesized as a precursor propeptide which is proteolytically processed to the active hormone, then degraded, by as yet unknown enzymatic pathways. Unstimulated brain-derived microvessels, primary cells and cell lines, all secreted bioactive IL-6. Cell lines secreted IL-6 exclusively as a 25 kD peptide. In order to understand mechanisms regulating the secretion of IL-6 in cerebral endothelium, levels of IL-6 were measured in cell culture supernatants of brain-derived endothelial cells exposed to dexamethasone, forskolin or dibutyryl cAMP and inhibitors of serine-proteases. In primary cells an...