Glucocorticoid steroid treatment

Glucocorticoids are potent anti-inflammatories, regardless of the inflammation's cause; their primary anti-inflammatory mechanism is lipocortin-1 (annexin-1) synthesis. Lipocortin-1 both suppresses phospholipase A2 , thereby blocking eicosanoid production, and inhibits various leukocyte inflammatory events ( epithelial adhesion , emigration , chemotaxis , phagocytosis , respiratory burst , etc.). In other words, glucocorticoids not only suppress immune response, but also inhibit the two main products of inflammation, prostaglandins and leukotrienes . They inhibit prostaglandin synthesis at the level of phospholipase A2 as well as at the level of cyclooxygenase /PGE isomerase (COX-1 and COX-2), [29] the latter effect being much like that of NSAIDs , potentiating the anti-inflammatory effect.

GC pulse upregulates Anxa1 and Anxa6 through increased GR binding of their GRE sites. ( A ) Model of transactivation pathway linking GC action in muscle to regulation of Anxa1 and Anxa6 expression; dashed lines, interrogated interactions. ( B ) Anxa1 and Anxa6 were upregulated in the skeletal muscle (quadriceps) and primary myoblasts (isolated from tibialis anterior) of mice 24 hours after a single pulse of GC steroids. ( C ) Twenty-four hours after a single GC pulse in C2C12 cells, ChIP-qPCR analysis showed that GRE sites of Anxa1 and Anxa6 were significantly enriched in GR occupancy as compared with vehicle. ( D ) Diagram shows experimental design of electroporation into muscles and 24 hours after . prednisone pulse in WT mice. ( E ) Histograms show that prednisone pulse upregulated luciferase activity when constructs contained the GRE sites (white bars). Conversely, GC-related upregulation was ablated after deletion of the GRE-binding site in the constructs (black bars). Klf15 GRE was monitored as positive control. Data are expressed as fold change to luminescence from vehicle-treated muscles electroporated with the same plasmids (dashed line). n = 5 mice/group ( B ); n = 4 assays or mice/group ( C and D ). * P < vs. vehicle, 1-way ANOVA test with Bonferroni’s multiple comparison ( B and C ); * P < vs. WT site construct, unpaired 2-tailed t test with Welch’s correction ( D ).

Glucocorticoid steroid treatment

glucocorticoid steroid treatment

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