The p38 mitogen-activated protein kinase pathway plays a critical role in PAR2-induced endothelial IL-8 production and leukocyte adhesion

Shiow L. Pan, Kai Y. Tao, Jih H. Guh, Hui L. Sun, Der Y. Huang, Ya L. Chang, Che M. Teng

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

A member of a new subfamily of G protein-coupled receptors, protease-activated receptor 2 (PAR2), is highly expressed on endothelial cells and plays an important role in inflammation. The purpose of this study was to determine the molecular mechanism used by PAR2 to induce IL-8 production and thereby mediate cell adhesion. We observed that PAR2-activating peptide (PAR2-AP) significantly increase peripheral blood mononuclear cells adhere to endothelial cells. Both PAR2-AP and the endogenous PAR2 activator trypsin caused concentration- and time-dependent increase in endothelial IL-8 production, and this effect was concentration dependency and selectively attenuated by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. Western blotting analysis showed that PAR2-AP induced phosphorylation of p38 MAPK and its upstream protein kinase MAPK kinase 3/6 (MKK3/6) in a time-dependent manner. Using reverse-transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, PAR2-AP was found to cause an increase in IL-8 mRNA expression and its transcription factor activating transcription factor 2, respectively,. As expected, these signals were suppressed by SB203580 in a concentration-dependent manner. Furthermore, introduction of dominant-negative vectors targeting p38 MAPK, MKK3, and MKK6 abolished PAR2-AP-mediated IL-8 production and cell adhesion function. In conclusion, PAR2 via p38 MAPK signaling regulates IL-8 production and thereby mediates cell adhesion.

Original languageEnglish
Pages (from-to)496-502
Number of pages7
JournalShock
Volume30
Issue number5
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

Fingerprint

PAR-2 Receptor
p38 Mitogen-Activated Protein Kinases
Interleukin-8
Leukocytes
Cell Adhesion
MAP Kinase Kinase 6
MAP Kinase Kinase Kinase 3
Activating Transcription Factor 2
Endothelial Cells
Protein Kinase Inhibitors
G-Protein-Coupled Receptors
Reverse Transcriptase Polymerase Chain Reaction
Trypsin
Protein Kinases
Blood Cells
Transcription Factors
Western Blotting
Enzyme-Linked Immunosorbent Assay
Phosphorylation
Inflammation

Keywords

  • Cell adhesion
  • Endothelial cells
  • Inflammation
  • PAR2

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

The p38 mitogen-activated protein kinase pathway plays a critical role in PAR2-induced endothelial IL-8 production and leukocyte adhesion. / Pan, Shiow L.; Tao, Kai Y.; Guh, Jih H.; Sun, Hui L.; Huang, Der Y.; Chang, Ya L.; Teng, Che M.

In: Shock, Vol. 30, No. 5, 11.2008, p. 496-502.

Research output: Contribution to journalArticle

Pan, Shiow L. ; Tao, Kai Y. ; Guh, Jih H. ; Sun, Hui L. ; Huang, Der Y. ; Chang, Ya L. ; Teng, Che M. / The p38 mitogen-activated protein kinase pathway plays a critical role in PAR2-induced endothelial IL-8 production and leukocyte adhesion. In: Shock. 2008 ; Vol. 30, No. 5. pp. 496-502.
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