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Trypsin induces tumour necrosis factor‐α secretion from a human leukemic mast cell line

2003; Wiley; Volume: 21; Issue: 2 Linguagem: Inglês

10.1002/cbf.1014

1099-0844

Ok‐Hwa Kang, Hyun‐Ja Jeong, Dae‐Ki Kim, Suck Chei Choi, Tae Hyun Kim, Yong‐Ho Nah, Hyung‐Min Kim, Young‐Mi Lee,

Coagulation, Bradykinin, Polyphosphates, and Angioedema

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‐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 n m ), SLIGKV‐NH 2 (100 μ m , corresponding to the PAR2 tethered ligand), or GYPGQV‐NH 2 (100 μ m , 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 μ m 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. Copyright © 2003 John Wiley & Sons, Ltd.