Anti-inflammatory mechanism of PPARγ on LPS-induced pulp cells: Role of the ROS removal activity

Abstract Objectives PPARγ has an anti-inflammatory effect on LPS-induced pulpal inflammation by decreasing the expression of MMPs, ICAM-1 and VCAM-1. However, the anti-inflammatory mechanism of PPARγ on the cell adhesion molecules and their upper signal pathways has not been clarified in pulp cells. The aim of this study is to investigate the anti-inflammatory mechanism of PPARγ in pulpal inflammation. Methods Human dental pulp cells (HDPCs) were isolated from freshly extracted third molar and cultured. The over-expression of PPARγ was used by adenoviral PPARγ (Ad/PPARγ). The formation of ROS was analysed using DCFH-DA with FACS, and NO was analysed using colorimetric bioassay. The expression of inflammatory molecules and inflammatory mechanism of PPARγ involved signal pathway were determined by immunoblotting. Results LPS-induced HDPC decreased PPARγ expression gradually and strongly activated the ERK1/2 signals amongst the MAPK, and induced NF-κB translocation from the cytosol to the nucleus. On the other hand, the cells to restore PPARγ with Ad/PPARγ were inhibited ERK1/2 despite being stimulated with LPS. In addition, the cells treated with rosiglitazone (PPARγ agonist) also were inhibited ERK1/2 activation, and the expression of ICAM-1, VCAM-1 and NF-κB translocation under LPS stimulation. The GW9667 (PPARγ antagonist)-treated HDPC did not affect the adhesion molecules and signal activation. LPS-induced HDPC produced significant NO and ROS levels, but their production was attenuated in the PPARγ over-expressed cells. Overall, the PPARγ effect under LPS stimulation is due to the removal activity of cellular NO and ROS formation. Conclusion These results suggest that anti-inflammatory mechanism of PPARγ is due to the removal activity of NO and ROS, and its removal effect suppressed ERK1/2 signal activation and NF-κB translocation. Therefore, the NO and ROS removal activity of PPARγ suggests major anti-inflammatory mechanism in HDPC, and it might offer us a possible molecule for various types of inflammatory inhibition.