Rosiglitazone pretreatment influences thrombin-induced phagocytosis by rat microglia via activating PPARγ and CD36.

OBJECTIVE: To explore the protective role of rosiglitazone against secondary brain injury after cerebral hemorrhage, we investigated the effect of rosiglitazone pretreatment on thrombin-induced microglial phagocytosis and described the molecular mechanisms involved in this process.

METHODS: Primary microglial cells were obtained from the brain tissue of newborn Sprague-Dawley rats and were randomly divided into four groups: the normal, thrombin stimulation, thrombin-treated plus rosiglitazone, and thrombin-rosiglitazone plus proliferator-activated receptor-gamma (PPARγ) antagonist groups. Microglial phagocytosis was measured using a laser scanning confocal microscope. The expression of PPARγ and cluster of differentiation 36 (CD36) in each group was detected via quantitative reverse transcription-PCR and western blot analysis.

RESULTS: The thrombin-treated plus rosiglitazone group showed a significant increase in phagocytic activity compared to the other groups (P<0.05), while the PPARγ antagonist group significantly reduced microglial phagocytosis compared to the thrombin-treated plus rosiglitazone and the normal group. Moreover, the expression of PPARγ and CD36 was considerably higher in the thrombin-treated plus rosiglitazone group than in the normal and the thrombin group. Nevertheless, the thrombin-rosiglitazone-PPARγ group expressed a lower level of PPARγ and CD36 compared to the thrombin-treated plus rosiglitazone group.

CONCLUSION: Rosiglitazone can increase thrombin-induced microglial phagocytosis, by a mechanism possibly involved in the increase of PPARγ and CD36 through the PPARγ pathway, which may provide a new option for cerebral hemorrhage treatment.