We extracted the total RNA and analyzed it by real time PCR. We found that dexamethasone alone increased PTEN mRNA expression, whereas treatment with anacardic acid attenuated the dexamethasone induced up regulation of PTEN mRNA, indicat ing that histone acetylation inhibition is involved in the dexamethasone induced PTEN expression. Discussion OVA induced asthma mice model is widely used for study of human asthma because of resemblance pathology and pathophysiology. Based on this model, we confirmed that PTEN proteins were under expressed in mice with OVA induced asthma. We also found that treatment of these mice with dexamethasone resulted in the restoration of PTEN expression. In vitro studies using human lung epithe lial cell A549 revealed that dexamethasone was able to increase both PTEN promoter activity and gene expression.

Data from all these assays together suggest that the effect of glucocorticoids on asthma may partly pass through the PTEN signaling pathway, and that PTEN is a new target gene involved in the response to dexamethasone. Although PTEN is a highly conserved gene with more than 80% iden tity in the promoter region between Homo sapiens and Mus musculus, more valuable data may be derived from humans. Thus, further studies in asthma patients is necessary. The mechanisms of glucocorticoids in anti inflamma tory treatment for asthma have been investigated exten sively. These studies were focused on different targets of airway or different gene expression, and had provided some answers regarding the mechanisms.

The target cells studied for glucocorticoid action were mainly air way epithelial cells, airway smooth muscle cells, and inflammatory cells, such as mast cells and monocytes. All these effects could also be divided into genomic and non genomic mechanisms depending on gene expression. More studies will continue to draw a full picture of the mechanisms of glucocorticoids in asthma therapy. Here a new mechan ism is proposed glucocorticoids up regulate PTEN tran scription, and PTEN, in turn, inhibits inflammation. As described above, PTEN maybe a target for asthma treatment. Regulation of PTEN expression is a key for this therapy. PTEN regulation has been the subject Brefeldin_A of many studies. Recent studies revealed that sim vastatin, pravastatin, fluvastatin, dietary exposure to the 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 of the scorpion Buthus martensii Karsch upregulates the expression of PTEN, accompanied by decreased levels of Akt and Bad phosphorylation. However, TGF b1, estrogen, and PRL 3 could down regulate PTEN expres sion. There are few reagents that can specifically regulate PTEN expression in the airways. We believe more efforts should be made in this area.