The mechanisms of glucocorticoids in anti inflammatory treatment for asthma have already been investigated extensively. These research were targeted on various targets of airway or unique gene expression, and had presented some answers pertaining to the mechanisms. The target cells studied for glucocorticoid action have been largely airway epithelial cells , airway smooth muscle cells , and inflammatory cells, such as mast cells and monocytes . All these results could also be divided into genomic and non genomic mechanisms based on gene expression . Far more research will carry on to draw a total picture of the mechanisms of glucocorticoids in asthma therapy. Here a fresh mechanism is proposed: glucocorticoids up regulate PTEN transcription, and PTEN, in turn, inhibits irritation. As described above, PTEN perhaps a target for asthma treatment. Regulation of PTEN expression is actually a vital for this treatment. PTEN regulation is the subject of numerous studies . Recent studies unveiled that simvastatin, pravastatin, fluvastatin, dietary publicity to your soy isoflavone genistein and phytoestrogens induce PTEN expression in mammary epithelial cells in vivo and in vitro .
Trichostatin A could up regulate PTEN transcription . The venom with the scorpion Buthus martensii Karsch upregulates the expression of PTEN, accompanied by decreased levels of Akt and Lousy phosphorylation . However, TGF b1, estrogen, and PRL 3 could down regulate PTEN expression . You will find few reagents that could specifically regulate PTEN expression from the airways. We think chemical library selleck chemicals a lot more efforts should be created in this area. With respect for the regulation inflammatory genes, glucocorticoids raise gene expression via alterations in chromatin structure by histone acetylation and recruitment of RNA polymerase II to the promoter webpage. This, in turn, effects during the activation of gene transcription . We’ve examined whether or not histone acetylation participates during the regulation of dexamethasone induced PTEN transcription.
As shown MDV3100 clinical trial in Figure three, the histone acetylase inhibitor anacardic acid inhibited dexamethasone induced PTEN up regulation in mRNA levels, indicating that histone acetylase inhibition is associated with transcriptional stimulation of the PTEN gene by dexamethasone. Our final results are supported from the findings of Ito et al. that substantial concentrations dexamethasone create a time and concentration dependent maximize in histone acetylation in A549 cells, leading to the recruitment of your activated transcription complex, and the subsequent boost from the expression of a few genes. The direct result of glucocorticoids on transcript activation occurs through binding and activation glucocorticoid receptors , which benefits during the translocation of glucocorticoid receptor complexes towards the nucleus and binding to glucocorticoid response factors in the promoter area of target genes .