Trypsin induces tumour necrosis factor-alpha secretion from a human leukemic mast cell line |
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Authors: | Kang Ok-Hwa Jeong Hyun-Ja Kim Dae-Ki Choi Suck-Chei Kim Tae-Hyun Nah Yong-Ho Kim Hyung-Min Lee Young-Mi |
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Institution: | Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Chonbuk, 570-749, South Korea. |
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Abstract: | Trypsin activating both proteinase-activated receptor (PAR) 2 and PAR4 plays an important role in inflammation. We have investigated the potential of trypsin to induce TNF-alpha secretion from the human leukemic mast cell line (HMC-1). HMC-1 cells co-express both PAR2 and PAR4, and their agonist trypsin signals to HMC-1 cells. Trypsin (100 nm), SLIGKV-NH(2) (100 microm, corresponding to the PAR2 tethered ligand), or GYPGQV-NH(2) (100 microm, corresponding to the PAR4 tethered ligand) induced tumour necrosis factor (TNF)-alpha secretion from HMC-1 cells. TNF-alpha secretion by trypsin was significantly blocked by pretreatment with 50 microm PD098059, MEK-1 inhibitor. Furthermore, trypsin stimulated the activation of extracellular signal-regulated kinase (ERK) in HMC-1 cells without any detectable activation of c-Jun N-terminal kinase (JNK) and p38 MAP kinase homologue. These results show that trypsin may induce TNF-alpha secretion following activation of ERK via both PAR2 and PAR4 on HMC-1 cells. |
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Keywords: | PAR2 PAR4 HMC‐1 TNF‐α MAPK trypsin |
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