β2-Adrenoceptor Agonists, Like Glucocorticoids, Repress Eotaxin Gene Transcription by Selective Inhibition of Histone H4 Acetylation

摘要: Eotaxin is a potent eosinophil chemoattractant implicated in various allergic inflammatory conditions including asthma, but relatively little known about its regulation. Human airway smooth muscle cells are an important source of eotaxin the airway. We have previously demonstrated that β2-adrenoceptor agonists (β2-agonists) and glucocorticoids additively inhibit production human cells, underlying mechanisms unclear. Here, we studied molecular their actions interactions on gene transcription. TNF-α-induced transcription was mediated mainly by factor NF-κB (p65/p50) as analyzed luciferase reporter assay, Western blotting, EMSA, electrophoretic mobility supershift assay. Chromatin immunoprecipitation assay TNF-α also induced selective histone H4 acetylation lysines 5 12 at promoter site p65 binding to promoter, resulting The inhibition β2-agonists transcriptional not due altered nuclear translocation or vitro capability, vivo promoter. Additive achieved when two groups drugs were combined. Our findings reveal novel mechanism which β2-agonists, like glucocorticoids, regulate NF-κB-mediated expression through acetylation. This provides one explanation for benefits result these agents combined treat may implications wide range diseases.