사람별아교세포주에서의 단백분해효소 활성 수용체-2를 매개한 TNF-α 의 분비

Abstract

Background : Proteinase-activated receptor 2 (PAR2) is cleaved, and it is activated by trypsin or mast cell tryptase. PAR2 plays an important role in inflammation. The aim of this study is to examine the potential of PAR2 agonists to modulate TNF-α secretion from the human astrocytoma cell line CCF-STTG1. Methods : PAR2 expression in CCF-STTG1 was examined using reverse transcriptase polymerase chain reaction and immunocytochemistry. The potential of PAR2 agonists to modulate TNF-α secretion from CCF-STTG1 was examined by enzymelinked immunosorbent assays. Results : CCF-STTG1 expresses PAR2. PAR2 agonists such as trypsin, mast cell tryptase, and activating peptide SLIGKV-NH2 (corresponding to the PAR2 tethered ligand) directly signal CCF-STTG1 to induce the secretion of TNF-α , but not in the case of the soybean trypsin inhibitor (SBTI) or VKGILS-NH2 (control peptide). Furthermore, the secretion of TNF-α was significantly reduced in CCF-STTG1 cells pre-treated with either 50 μM PD98059 (mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor) or 1 μM SB203580 (p38 MAPK inhibitor) 30 min before trypsin stimulation. Conclusions : These results show that trypsin may induce TNF- secretion through the activation of MEK and p38 MAPK via PAR2 in astrocytoma cell line CCF-STTG1.