| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
I investigated expression of protease-activated receptor(PAR) on both human esophageal and gastric epithelial cells, and mechanisms of PAR-mediated cytokine production from these cultured cells.
1.PAR-1 and PAR-2 were constitutively expressed on unstimulated cultured esophageal (HEEL) and gastric (MKN-45) epithelial cells. In addition, PAR-1 and PAR-2 were stained in the esophageal and gastric mucosa obtained from human biopsy materials.
2.PAR-1 agonist (thrombin) and PAR-2 agonist (trypsin and tryptase) resulted in induction of IL-8 production from HEEC and MKN-45 cells time- and dose- dependently.
3.Increased IL-8 production was significantly by antibody to PAR, MAPK inhibitor and transfection of NFkappaB or AP-1 mutant vector.
These data indicate that serine proteases, such as thrombin, trypsin or tryptase, promote IL-8 production from cultured esophageal and gastric epithelial cells, which mechanisms are associated with activation of protease-activated receptor, G-protein coupled receptor, followed by the activation of MAPK(p-38, JNK, ERK1/2) and transcription factor (NFkappaB, AP-1). These results suggest that trypsin which comes in esophagus and stomach from duodenum and tryptase derived from mast cells in the gastrointestinal mucosa may be related to mucosal injury via PAR-activated IL-8 production.
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