Biomaterial Database

Glucocorticoid inhibition of interleukin-1-induced interleukin-6 production by human lung fibroblasts: evidence for transcriptional and post-transcriptional regulatory mechanisms. 1994

R J Zitnik, and N L Whiting, and J A Elias

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510-8057.

Interleukin (IL)-6 is a pleiotropic cytokine produced by a wide variety of cells including fibroblasts, macrophages, endothelial cells, and T and B lymphocytes. Regulated IL-6 production is an important part of normal biologic homeostasis, and abnormal IL-6 production has been associated with a large number of diseases including asthma and lung allograft rejection. Glucocorticoids are potent anti-inflammatory agents that are widely used to suppress pulmonary inflammation. To further understand the mechanisms underlying this inhibition, we determined whether glucocorticoid compounds regulate human lung fibroblast IL-6 production and characterized the mechanisms of the effects that were noted. These studies demonstrate that glucocorticoids inhibit IL-1-induced IL-6 production in a dose-dependent fashion. A greater than 95% decrease in IL-6 production was seen with 10(-6) and 10(-7) M dexamethasone, prednisolone, and hydrocortisone, and IC50 values for these agents were approximately 5 x 10(-10), 5 x 10(-9), and 10(-8) M, respectively. mRNA analysis demonstrated that these alterations in protein production were associated with proportionate decreases in IL-6 mRNA accumulation, and that this suppression of IL-6 mRNA could be reversed by the glucocorticoid receptor antagonist RU 486. Nuclear run-on studies demonstrated that glucocorticoids inhibit-IL-1-induced IL-6 gene transcription. However, the magnitude of this effect could not fully account for the potency of the glucocorticoid-induced alterations in IL-6 mRNA accumulation and protein production since 10(-6) M dexamethasone caused only a 50% decrease in IL-1-induced IL-6 gene transcription.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D007375	Interleukin-1	A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.	IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D011239	Prednisolone	A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.	Di-Adreson-F,Predate,Predonine,Di Adreson F,DiAdresonF
D011965	Receptors, Glucocorticoid	Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example.	Corticoid Type II Receptor,Glucocorticoid Receptors,Glucocorticoids Receptor,Corticoid II Receptor,Corticoid Type II Receptors,Glucocorticoid Receptor,Receptors, Corticoid II,Receptors, Corticoid Type II,Receptors, Glucocorticoids,Corticoid II Receptors,Glucocorticoids Receptors,Receptor, Corticoid II,Receptor, Glucocorticoid,Receptor, Glucocorticoids
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast
D005938	Glucocorticoids	A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.	Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006854	Hydrocortisone	The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.	Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol