Trypsin induces tumour necrosis factor-α 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-α 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-NH₂ (100 μM, corresponding to the PAR2 tethered ligand), or GYPGQV-NH₂ (100 μM, corresponding to the PAR4 tethered ligand) induced tumour necrosis factor (TNF)-α secretion from HMC-1 cells. TNF-α secretion by trypsin was significantly blocked by pretreatment with 50 μM 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-α secretion following activation of ERK via both PAR2 and PAR4 on HMC-1 cells.