Statins synergize dexamethasone-induced adipocyte fatty acid binding protein expression in macrophages
Hu W et al. – This study defines an important mechanism involved in the regulation of macrophage FABP4 expression by a glucocorticoid and statins.Methods
- Authors determined the effect of co–treatment of statins and dexamethasone on macrophage FABP4 expression.
- Unexpectedly, statins did not block the induction of macrophage FABP4 expression by dexamethasone.
- In contrast, statins synergized dexamethasone–induced FABP4 expression.
- In vivo, pitavastatin synergized dexamethasone–induced FABP4 expression in both peritoneal macrophages and adipose tissues.
- Cholesterol and mevalonate, but not farnesylation and geranylgeranylation, inhibited the synergistic induction.
- Promoter assay disclosed a putative negative glucocorticoid regulatory element (nGRE) in FABP4 gene.
- Pitavastatin had little effect on expression of glucocorticoid receptor (GR).
- However, pitavastatin enhanced dexamethasone–mediated GR nuclear translocation but inhibited the binding of GR with nGRE.