Proinflammatory actions of glucocorticoids: glucocorticoids and TNFα coregulate gene expression in vitro and in vivo.

ABSTRACT: Synthetic glucocorticoids are widely used for treatment of many inflammatory diseases. However, long-term glucocorticoid treatment can cause a variety of negative side effects. A genome-wide microarray analysis was performed in human lung A549 cells to identify genes regulated by both the antiinflammatory steroid dexamethasone (Dex) and the proinflammatory cytokine TNFα. Unexpectedly, we discovered that numerous genes were coregulated by treatment with both Dex and TNFα. We evaluated the mechanism of coregulation of one of these genes, serpinA3 (α-1 antichymotrypsin), a secreted, acute phase protein strongly associated with numerous inflammatory diseases. Up-regulation of serpinA3 requires the presence of both the glucocorticoid receptor and TNFα soluble receptor 1. Treatment with Dex or T

SUBMITTER: Lannan EA 

PROVIDER: S-EPMC3404340 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature