Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-6 (IL-6) is the end-product of a cytokine signaling cascade and is secreted by specialized immune cells during inflammation. It has a great influence on many functions, including differentiation, stimulation, and activation of immune cells, or other cells of neuroendocrine origin. Thus, IL-6 serves as a key messenger in its communication with the neuroendocrine system, and serves as a potent activator of the hypothalamic-pituitary-adrenal axis at all levels. Changes in the levels of expression of this cytokine and its receptor have been observed during chronic inflammatory disease, and have been associated with tumorigenesis. Therefore, we studied the effect of IL-6 on normal and adenomatous human adrenal cells in vitro. The expression of IL-6 receptor mRNA was quantified within the same tissue. IL-6 potently stimulated cortisol secretion from dispersed normal human adrenal cells. We found immunoreactivity for the IL-6 receptor on cultured cells and paraffin-embedded sections of adrenal tissues. Further, there was a more pronounced expression of IL-6 mRNA in adrenal adenomas of patients with Cushing's syndrome, compared to normal human adrenals. Despite this fact, the sensitivity of cells of adenomatous adrenal glands to IL-6 was significantly decreased relative to cells from normal controls. These results were confirmed employing the permanent adrenocortical cancer cell line model NCI-H295. We infer that the loss of responsivity of tumorous adrenal cells to IL-6, and in part corticotropin, is an important step in the process of adrenal tumorigenesis by which regulation by differentiating proteins is bypassed.
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PMID:Role of interleukin-6 in stress response in normal and tumorous adrenal cells and during chronic inflammation. 1211 87

The mean blood content of interleukin-6 in patients with adrenal tumors was much higher than in healthy donors. No correlations were revealed between interleukin-6 level, patients sex and age, stage and duration of the disease. Interleukin-6 concentration was maximum in patients with adrenocortical cancer. A negative correlation was found between interleukin-6 level and blood cortisol concentration in patients with cortisol-producing adenoma. In patients with aldosterone-producing adenoma, interleukin-6 level tended to correlate negatively with plasma renin activity.
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PMID:Serum interleukin-6 in patients with adrenal tumors. 1523 38

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.
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PMID:The endothelium secretes interleukin-6 (IL-6) and induces IL-6 and aldosterone generation by adrenocortical cells. 1877 60