{'fraction_non_alphanumeric': 0.054221533694810226, 'fraction_numerical': 0.05112316034082107, 'mean_word_length': 5.835978835978836, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
IL‐8 release triggered by proteinase‐activated receptor‐2 stimulation involves both MEK/ERK and PI3 kinase/Akt pathways in gastrointestinal epithelial cells

In the gastrointestinal (GI) system, proteinase‐activated receptor‐2 (PAR2) is widely expressed and involved in inflammatory responses. In the present study, we examined and characterized release of interleukin‐8 (IL‐8), a pro‐inflammatory cytokine, following PAR2 activation in human colorectal cancer‐derived HCT‐15 cells and human gastric adenocarcinoma‐derived MKN‐45 cells. A PAR2‐activating peptide (PAR2‐AP), but not a PAR2‐inactive scrambled peptide or a PAR1‐AP, induced IL‐8 release in these GI epithelial cells in 24 h. The PAR2‐triggered IL‐8 release was suppressed by inhibitors of MEK (U0126) or PI3 kinase (LY294002), but not by inhibitors of JNK (SP600125), p38 MAP kinase (SB206580), tyrosine kinase (genistein), EGF receptor tyrosine kinase (PD153035) or NF‐κB (PDTC). PAR2 stimulation actually induced phosphorylation of ERK and Akt. U0126 suppressed the phosphorylation of ERK, but not Akt, and LY294002 suppressed the phosphorylation of Akt, but not ERK. These results suggest that, in the GI epithelial cells, activation of PAR2 triggers release of IL‐8 via two independent pathways, MEK/ERK and PI3 kinase/Akt.