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KMID : 0357920030370030159
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Korean Journal of Pathology
2003 Volume.37 No. 3 p.159 ~ p.165
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Secretion of TNF-alpha via Proteinase-Activated Receptor-2 in Human Astrocyte Cell Line
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Kim Mi-Sun
Kim Jin-Ah
Kang Ok-Hwa
Baek Ok-Seon
Um Jae-Young
Yi Jin-Mu
Yun Ki-Jung
Kim Hyung-Min
Lee Young-Mi
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Abstract
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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-alpha 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-alpha secretion from CCF-STTG1 was examined by enzyme-linked 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-alpha, but not in the case of the soybean trypsin inhibitor (SBTI) or VKGILS-NH(2) (control peptide). Furthermore, the secretion of TNF-alpha was significantly reduced in CCF-STTG1 cells pre-treated with either 50 micro M PD98059 (mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor) or 1 micro M SB203580 (p38 MAPK inhibitor) 30 min before trypsin stimulation.
Conclusion: These results show that trypsin may induce TNF-alpha secretion through the activation of MEK and p38 MAPK via PAR2 in astrocytoma cell line CCF-STTG1.
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KEYWORD
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Proteinase, Activated Receptor 2, Trypsin, Tumor Necrosis Factor, alpha-Cytokines, Astrocytoma Cell Line
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