Trypsin induces tumour necrosis factor-alpha secretion from a human leukemic mast cell line.
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.
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Chonbuk, 570-749, South Korea.
Ok-Hwa
OH
Kang
Hyun-Ja
HJ
Jeong
Dae-Ki
DK
Kim
Suck-Chei
SC
Choi
Tae-Hyun
TH
Kim
Yong-Ho
YH
Nah
Hyung-Min
HM
Kim
Young-Mi
YM
Lee
D015550:Cell Degranulation / Q000502:physiology; D006801:Humans; D007946:Leukemia, Mast-Cell / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000096:biosynthesis / Q000235:genetics; D018179:Receptors, Thrombin / Q000096:biosynthesis / Q000235:genetics; D014357:Trypsin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D014357:Trypsin; C112908:protease-activated receptor 4