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Fibroblast-Pneumonocyte Factor
Published in Jason Kelley, Cytokines of the Lung, 2022
Glucocorticoid acts on the lung by the classic glucocorticoid receptor mechanism (Ballard et al., 1984; Gross et al., 1983). Glucocorticoids bind to cytosolic glucocorticoid receptors (GR) that are then translocated to the nucleus, where they bind to glucocorticoid response elements, which leads to the induction or repression of gene transcription (Evans, 1988; Miesfeld, 1990). The GR gene expression in whole fetal rat lung is developmentally regulated (Sweezey et al., 1989). The GR mRNA levels are relatively low on day 18 of fetal development. On gestational day 19, there is a short-lived, dramatic enhancement of GR mRNA content, abruptly followed (days 20–22) by a return of the mRNA to levels present before day 19. Immediately after day 19, there is a gradual and sustained rise in GR-binding activity, suggesting a pretranslational stimulation of GR production. The increase in GR number in fetal rat lung is not associated with any apparent change in affinity for ligand (Ballard et al., 1984; Brönnegard and Okret, 1988). This developmentally timed enhancement of GR gene expression occurs concomitantly with a rise in plasma glucocorticoid levels (Gonzales and Ballard, 1989). This parallel rise in rat lung GR number and in the mRNA and circulating glucocorticoid levels suggests that, in the fetus, glucocorticoids do not regulate lung GR gene expression by a feedback down-regulatory mechanism. Indeed, maternal administration of glucocorticoids increases the GR mRNA level in the fetal lung (Sweezey et al., 1990).
General Surgery
Published in Tjun Tang, Elizabeth O'Riordan, Stewart Walsh, Cracking the Intercollegiate General Surgery FRCS Viva, 2020
Rebecca Fish, Aisling Hogan, Aoife Lowery, Frank McDermott, Chelliah R Selvasekar, Choon Sheong Seow, Vishal G Shelat, Paul Sutton, Yew-Wei Tan, Thomas Tsang
If the CT was normal and a CXR showed a small-cell lung cancer, do you know how you could control the symptoms?Metyrapone, Ketoconazole and Mitotane will reduce circulating cortisol levels. These agents inhibit adrenal steroidogenesis at various enzymatic steps. As monotherapy they have been shown to be effective in approximately 50% of patients. There are limited data on combined therapy.Glucocorticoid receptor antagonists provide a different mechanism of action to reduce cortisol action. Mifepristone has been approved for the treatment of hyperglycaemia in patients with Cushing's syndrome.
Hormones as Immune Modulating Agents
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
In the spleen and thymus of adrenalectomized rats, type II adrenal steroid receptor binding was significantly increased; it could be blocked by aldosterone administration. This indicates that type I receptors may play a tonic inhibitory role in type II receptor expression in immune cells which express both receptor subtypes [235]. The effect of selective type I and type II adrenal steroid receptor agonists on lymphocyte distribution in the peripheral blood and spleen of young adult rats has been studied. The type II receptor agonist RU48362 decreased T and B cell and natural killer cell numbers to a very low absolute level. Aldosterone, which is a type I receptor agonist, significantly reduced the number of lymphocytes and monocytes and, unlike RU48362, also decreased the number of neutrophils. T helper cells and NK cells were decreased by aldosterone, but there was no effect on B cells and T suppressor/cytotoxic cells. Corticosterone at physiological doses behaved as a type II receptor agonist in these experiments [236], The response of spleen cells from adrenalectomized animals to concanavalin A was stimulated by pretreatment for 10–13 min to low concentrations (3–30 mM) of aldosterone if RU48362 was also present. Corticosterone had a similar effect. These effects became evident in the presence of glucocorticoid receptor antagonist and after short corticosteroid exposure times. After prolonged preincubation with high concentrations of corticosteroids, an immunosuppressive effect was observed [237].
Glucocorticoid receptors involved in ginsenoside compound K ameliorate adjuvant arthritis by inhibiting the glycolysis of fibroblast-like synoviocytes via the NF-κB/HIF-1α pathway
Published in Pharmaceutical Biology, 2023
Yating Wang, Xiurong Bao, Hao Xian, Fang Wei, Yining Song, Siyu Zhao, Yujie Zhang, Yumeng Wang, Ying Wang
Glucocorticoids are steroid hormones that show potent anti-inflammatory actions via glucocorticoid receptors (GR) and are widely employed in clinical settings. As a transcription factor, the activated GR can activate or suppress the expression of a vast number of target genes through transactivation and transrepression, including many genes responsible for anti-inflammatory and proinflammatory responses. Although glucocorticoids have excellent anti-inflammatory properties, long-term and high-dose usage of glucocorticoids frequently result in osteoporosis and a variety of other side effects, which are mostly due to GR transactivation (Sundahl et al. 2015). In our results, radiography analysis of rat joints demonstrated that dexamethasone (Dex), a traditional glucocorticoid, reduced bone density of local joints despite being anti-inflammatory, whereas CK had both anti-inflammatory and bone-protective effects.
The protective effect of N-acetyl cysteine against selenium toxicity and gamma irradiation in rats
Published in Drug and Chemical Toxicology, 2023
Riham Abdel-Hamid Haroun, Nahed Abdel-Aziz, Soha Saad
Corticosterone is the main adrenal corticosteroid in laboratory rodents such as rats and mice as they lack the adrenal enzyme CYP17 and therefore cannot produce cortisol (Raff and Cort 2016). Corticosterone is the main stress hormone of the glucocorticosteroid group and secreted after the activation of the hypothalamic-pituitary-adrenal axis with environmental stressors (Sokół and Koziatek-Sadłowska 2020). This is consistent with our results; as corticosterone concentration was significantly increased in the rats after the exposure of rats to different stress (toxic dose of Se and IR); but when these rats treated with NAC before toxic dose of Se and IR, it was found that corticosterone was significantly decreased, improving the protective effect of NAC. Corticosterone initiates physical response to stress by binding to glucocorticoid receptor, which is transcribed from NR3C1 gene, thus promoting stress response (Gandhi et al. 2020). Previous studies reported the increased expression level of NR3C1 gene was associated with stress such as infection and inflammation (Sevilla and Pérez 2018, Iftimovici et al. 2020), which is consistent with our results as NR3C1 expression level was significantly increased in Rad group and Se group when compared to control group; while it was decreased in Rad + NAC group and Se + NAC group when compared to Rad group and Se group, indicating the protective effect of NAC against stress. Prevatto et al. (2017) found that NAC treatment induced downregulation of NR3C1, which is in agreement with our results.
The role of systemic corticosteroids in severe asthma and new evidence in their management and tapering
Published in Expert Review of Clinical Immunology, 2021
Francesco Menzella, Giulia Ghidoni, Matteo Fontana, Silvia Capobelli, Francesco Livrieri, Claudia Castagnetti, Nicola Facciolongo
Corticosteroids affect several steps in the inflammatory pathway. To exert their action, steroid molecules diffuse across cell membranes and bind to their receptors, causing their conformational change [8]. The glucocorticoid receptor complex moves to the cell nucleus, where it dimerizes and through the glucocorticoid response it activates genes that suppress or stimulate the protein transcription. These are termed transrepression or transactivation effects [9]. Thereafter, these agents inhibit transcription factors that control pro-inflammatory synthesis mediators, including eosinophils, macrophages, mast cells, lymphocytes and dendritic cells [10,11]. Another important action is the inhibition of phospholipase A2, which is responsible for the production of numerous pro-inflammatory mediators [12]. Corticosteroids inhibit genes responsible for expression of proinflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha (TNF-α) and other interleukins. Also, corticosteroids activate the upregulation of lipocortin and annexin A1, proteins that reduce the synthesis of prostaglandins and leukotrienes and which also inhibit the activity of cyclooxygenase-2 and reduce the migration of neutrophils to inflammatory sites [13].