PAR2-induced IL-8 production through p38 MAPK in HUVECs

• Main Authors: Kai-Yunn Tao, 陶楷韻
• Other Authors: 鄧哲明
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/15461820002965507300

碩士 === 國立臺灣大學 === 藥理學研究所 === 93 === Protease-activated receptor 2（PAR2）is the second member of a new subfamily of G protein-coupled receptors：the protease-activated receptors（PARs）. PAR2 is highly expressed on endothelial cells and plays an important role in inflammation and pain. In this study, we observed that the selective PAR2-activating peptide（PAR2-AP）could significantly induce the interleukin-8（IL-8）production in human umbilical vein endothelial cells（HUVECs）. Therefore, the signaling pathway involved in PAR2-induced endothelial IL-8 production was studied in this paper. Both the PAR2-AP and endogenous PAR2 activator, trypsin, caused concentration- and time-dependent increase of endothelial IL-8 production and this effect was concentration-dependently attenuated by the selective p38 mitogen-activated protein kinase（p38 MAPK）inhibitor, SB203580. Western blotting analysis showed that PAR2-AP induced the phosphorylation of p38 MAPK and its upstream and downstream protein kinases, including MAPK kinase 3/6（MKK3/6）, eIF–4E, Mnk-1 and MAPK-activated protein kinase-2（MAPKAPK-2）, in a time-dependent manner. SB203580 exhibited a significantly decreased phosphorylation of these protein kinases except for MAPKAPK-2. In addition, PAR2-AP caused an elevation of IL-8 mRNA expression and its transcription factor, activating transcription factor-2 activation. As expectedly, these signals were also suppressed by SB203580 in a concentration-dependent manner. Furthermore, introduction of dominant-negative vectors targeting on p38 MAPK, MKK3 and MKK6 resulted in abolishing the IL-8 production by PAR2-AP. In conclusion, our data suggest that the p38 MAPK pathway is important for PAR2-induced IL-8 production in HUVECs.