Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 377, Issue 2, Pages 622-626Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.10.018
Keywords
Proteinase-activated receptor-2 (PAR2); Interleukin-8 (IL-8); Inflammation; Gastrointestinal epithelial cell; MKN-45 cell; HCT-15 cell; ERK; PI3 kinase
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Proteinase-activated receptor-2 (PAR2) plays pro-inflammatory roles in many organs including the gastrointestinal (GI) tract. To clarify the downstream pro-inflammatory signaling of PAR2 in the GI tract, we examined interleukin-8 (IL-8) release and the underlying cellular signaling following PAR2 stimulation in human colorectal cancer-derived HCT-15 cells and human gastric adenocarcinoma-derived MKN-45 cells. A PAR2-activating peptide, but not a PAR2-inactive scrambled peptide or a PAR1 - activating peptide, caused IL-8 elease in these GI epithelial cells. The PAR2-triggered IL-8 release was suppressed by inhibitors of MEK (U0126) or PI3-kinase (LY294002), and PAR2 stimulation indeed activated the downstream kinases, ERK and Akt. U0126 blocked the phosphorylation of ERK, but not Akt, and LY294002 blocked the phosphorylation of Akt, but not ERK. Together, PAR2 triggers IL-8 release via two independent signaling pathways, MEK/ERK and PI3-kinase/Akt, suggesting a role of PAR2 as a pro-inflammatory receptor in the GI tract. (C) 2008 Elsevier Inc. All rights reserved.
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