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Updated: Sep 28, 2026

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
Agonists of proteinase-activated receptor 2 induce TNF-alpha secretion from astrocytoma cells
Mi-Sun Kim1, Hyun Jo, Jae-Young Um
1Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Cheonbuk 570-749, South Korea.
Abstract:
Proteinase-activated receptor 2 (PAR2) is cleaved and activated by trypsin or mast cell tryptase, and may play an important role in inflammation. We have investigated the potential of PAR2 agonists to modulate TNF-alpha secretion from human astrocytoma cell line CCF-STTG1. We found that CCF-STTG1 expresses PAR2 by RT-PCR and Western blot analysis. Agonists such as trypsin, the peptide SLIGKV-NH(2) (corresponding to the PAR2 tethered ligand), or mast cell tryptase directly signal to CCF-STTG1 to stimulate secretion of TNF-alpha but do not stimulate in the presence of soybean trypsin inhibitor (SBTI) or VKGILS-NH(2) (reverse peptide). The secretion of TNF-alpha by trypsin was significantly blocked by pretreatment with either 50 microM PD98059 or 1 microM SB203580. Furthermore, trypsin stimulated the activation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase homologue in CCF-STTG1 without any detectable activation of c-Jun N-terminal kinase (JNK). These results show that trypsin may induce TNF-alpha secretion following activation of ERK and p38 via PAR2 in CCF-STTG1.
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