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

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• 作者：Jae-Cheol Kim^a ; ^d ; Young-Hee Lee^b ; ^d ; Mi-Kyung Yu^c ; Nan-Hee Lee^b ; Jong-Duk Park^c ; Govinda Bhattarai^b ; Ho-Keun Yi^b ; ^{yihokn@chonbuk.ac.kr}
• 关键词：Pulpal inflammation ; PPAR纬 ; ERK1/2 ; NF-魏B ; NO ; ROS ; ICAM-1 ; VCAM-1
• 刊名：Archives of Oral Biology
• 出版年：2012
• 期刊代码：25_00039969
• 类别：med
• 出版时间：April, 2012
• 卷：57
• 期：4
• 页码：392-400
• 文件大小：890 K

摘要

Objectives

PPAR纬 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 PPAR纬 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 PPAR纬 in pulpal inflammation.

Methods

Human dental pulp cells (HDPCs) were isolated from freshly extracted third molar and cultured. The over-expression of PPAR纬 was used by adenoviral PPAR纬 (Ad/PPAR纬). 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 PPAR纬 involved signal pathway were determined by immunoblotting.

Results

LPS-induced HDPC decreased PPAR纬 expression gradually and strongly activated the ERK1/2 signals amongst the MAPK, and induced NF-魏B translocation from the cytosol to the nucleus. On the other hand, the cells to restore PPAR纬 with Ad/PPAR纬 were inhibited ERK1/2 despite being stimulated with LPS. In addition, the cells treated with rosiglitazone (PPAR纬 agonist) also were inhibited ERK1/2 activation, and the expression of ICAM-1, VCAM-1 and NF-魏B translocation under LPS stimulation. The GW9667 (PPAR纬 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 PPAR纬 over-expressed cells. Overall, the PPAR纬 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 PPAR纬 is due to the removal activity of NO and ROS, and its removal effect suppressed ERK1/2 signal activation and NF-魏B translocation. Therefore, the NO and ROS removal activity of PPAR纬 suggests major anti-inflammatory mechanism in HDPC, and it might offer us a possible molecule for various types of inflammatory inhibition.