Here ya go Epidural man:
Steroids bind to cytoplasmic GC receptors within target cells -> DNA binding proteins
Hormone binding site & DNA binding site are expressed in almost every type of cell
The inactive GR is bound to a large protein complex and folded into a conformation that Is optimal for binding and prevents the unoccupied receptor from entering the nucleus.
Once GC binds, GR complex dissociates & activated GC translocates to the nucleus -> binds to DNA at GC response elements (GREs) in the promoter sequences of target genes->GR expression regulates at transcriptional, translational, or post-translational levels. This mechanism appears to account for the effect of steroids on the transcription of collagenase. Collagenase transcription is induced by tumor necrosis factor a (TNFa) and phorbol esters, which activate apoprotein-1. The GR complex binds AP-1, forming a protein-protein complex and causing mutual repression of DNA binding. In another possible mechanism of inhibition of gene transcription, the GR enhances the transcription of specific ribonucleases that break down mRNA. Steroid administration blocks cytokine effects. Cytokines promotes prolonged eosinophil survival, increased adhesion molecule expression, potentiated eosinophil degranulation, and movement of eosinophils across and endothelial barrier leading to programmed cell death, or apoptosis. Expansion in the number of circulating neutrophils secondary to decreased adherence to vascular endothelium (demargination) and stimulation of bone marrow production. GCs interefere with T-cell mediated immunity. They inhibit production of T lymphocytes by downregulating T-cell growth factors IL-1B and IL-2, and inhibit the release of various T-lymphocyte cytokines. Potently inhibit inducible form of NOS in macrophages, and prevents the induction of NOS expression by endotoxin. (Cytokines induce nitric oxide synthase (NOS), -> ↑d nitric oxide production -> NO increases plasma exudation in inflammatory sites)
Adhesion Moleculesfacilitate trafficking of inflammatory cells to sites of inflammation
The expression of the adhesion molecules E-selectin, P-selectin, and intracellular adhesion molecule-1 on the surface of endothelial cells is induced by the cytokines IL-1β and TNF-α. They enable endothelium to recruit leukocytes actively and nonselectively (neurtrophils, eosinophils, mononuclear cells, and basophils). GCs are effective and potent inhibitors of TNF-alpha and IL-1 release from macrophages, monoctyes, and other infiltrating cells. Second class of cytokines that selectively activate the endothelium IL-4 & IL-13, two cytokines associated with allergic diseases. Inhibit plasma exudation from postcapillary venules at inflammatory sites. Delayed effect suggesting gene transcription & protein syntheses are involved: synthesis of vasocortin. GGs also stabilize lysosomal membranes -> inhibiting lysosomal enzyme release which prevents the sequestration of water intracellularly and swelling and destruction of cells. They inhibit leukocyte accumulation and complement-induced polymorphonuclear neutrophil (PMN) aggregation and ↓ PMN chemotaxis, T-cell and B-cell proliferation and the differentiation of macrophages. GGs also suppress spontaneous ectopic neural discharge originating in experimental neuromas prevent the later development of ectopic impulse discharge in freshly cut nerves. Effect appears to be mediated by a direct membrane-stabilizing action
rather than an antinflammatory action. Topical application of methylprednisolone noted to block transmission of C-fibers but not the A-beta fibers
Sorry I was bored
