Dexamethasone promotes IL-4-induced alternative activation at PPARγ point, instead of upstream STAT6 in BV2 microglial cells

Background Microglia are innate immune effector cells in the central nervous system and play an extremely important role in the physiological processes of the central nervous system. When microglia are activated, there are two polarization states, M1 and M2 phenotype. Dexamethasone is a glucocorticoid widely used in clinical practice, which pharmacological effects are mainly anti-inflammatory, anti-toxic. However, whether Dexamethasone affects polarization state of microglia is unknown. In this study, we investigate the effect of Dexamethasone on IL-4-induced alternative activation in murine BV-2 microglial cells. Methods BV-2 cells were incubated with Dexamethasone alone, IL-4 alone, or the combination of Dexamethasone and IL-4. Western blot and immunofluorescence were performed to detect protein levels of alternative activation markers arginase 1 (Arg1), found in inflammatory zone 1 (FIZZ1). Moreover, we investigated the effects of Dexamethasone on IL-4 induced activation of signal transducer and activators of transcription 6 (STAT6) and peroxisome proliferator-activated receptor-gamma (PPARγ). Results Dexamethasone promoted IL-4 induced microglia alternative activation by increasing the expression of Arg1 and FIZZ1. Dexamethasone also enhanced the expression of PPARγ. These effects were reversed by RU486 (a Dexamethasone antagonist). Further, the effects of Dexamethasone and IL-4 on Arg1 and FIZZ1 were blocked by the application of GW9662 (a PPARγ antagonist). Conclusions Our studies confirm that Dexamethasone promotes IL-4 induced alternative activation via STAT6/PPARγ signaling pathways in microglia. At the same time, it was confirmed that Dexamethasone acts on PPARγ instead of STAT6. These findings support that Dexamethasone has a therapeutic potential for neuroinflammatory diseases via alternative activation.