Conclusions Vandetanib Self negative regulation of phagocytosis by the phagocytic receptor can be useful in protecting phagocytes from ex cessive phagocytosis during extended exposure to particles that are destined for ingestion. In our study, the phagocytic receptor was CR3 and the ingested particles the tissue debris of degenerated myelin. Background Glucocorticoids are essential for the coordinated regula tion of metabolic and immune responses. They are well known due to their potent anti inflammatory and im mune suppressive effects, and therefore widely used in clinics to treat inflammatory and autoimmune diseases. Increasing evidence indicates that endogenously occur ring glucocorticoids can, in some situations, stimulate inflammation by enhancing the production of pro inflammatory mediators and promoting oxidative stress.
The underlying mechanisms and the role of cor ticosteroid receptors are, however, not fully understood. Glucocorticoids exert their effects mainly by activating glucocorticoid receptors and mineralocorticoid receptors. A comparison of corticosterone Inhibitors,Modulators,Libraries binding to MR and GR in rat hippocampal preparations revealed a 10 fold higher affinity for MR compared with GR. Importantly, hippocampal MR was occupied about 80% while GR was occupied 10% only if samples were taken at the nadir of the hypothalamus pituitary adrenal axis diurnal Inhibitors,Modulators,Libraries rhythm in the morning. GR Inhibitors,Modulators,Libraries binding increased at higher corticosterone levels, suggesting that GR is activated during stress and potentially also at diurnal peak levels.
Differential binding by MR and GR in various brain cells needs to be considered Inhibitors,Modulators,Libraries in order to under stand effects of glucocorticoids in the CNS. In classical mineralocorticoid target tissues involved in electrolyte and volume regulation, such as renal cortical collecting ducts, distal colon, and salivary and sweat glands, MR is co expressed with 11B hydroxysteroid dehydrogenase 2, which converts active into inactive glucocorticoids. The close proximity of 11B HSD2 and MR has been proposed to prevent MR activation by glucocorticoids, thereby render ing specificity of the receptor to aldosterone. Defi cient 11B HSD2 activity has been shown to result in sodium and water retention, causing edema formation and hypertension. To avoid these adverse effects caused by excessive activation Inhibitors,Modulators,Libraries of renal and intestinal MR, synthetic glucocorticoids selectively activating GR have been designed and are widely used in therapy of inflam matory and autoimmune diseases.
Besides, MR has important functions in vascular cells, adipocytes, osteocytes, neutrophils, dendritic cells, and macrophage. In the brain, MR plays an important role in hippocampal neurons and in immune cells. Glucocorticoids are essentially involved in the modulation of the coordinated action of monocytes, macrophages, astrocytes, and microglia cells etc during in flammation in the brain.