Inhibition of The Stem Cell Factor-Induced Migration of Mast Cells by Dexamethasone

  • Jeong, Hyun-Ja (Department of Pharmacology, College of Oriental Medicine, Kyung Hee University) ;
  • Hong, Seung-Heon (Department of Oriental Pharmacy, College of Pharmacy) ;
  • Park, Rae-Kil (VestibuloCochlear Research Center of Wonkwang University) ;
  • Kim, Hyung-Min (Department of Pharmacology, College of Oriental Medicine, Kyung Hee University)
  • Published : 2003.11.01

Abstract

Mast cells accumulation can be causally related with several allergic inflammations. Previous work has demonstrated that glucocorticoids decreased tissue mast cell number and stem cell factor (SCF)-induced migration of mast cells required p38 mitogen-activated protein kinase (MAPK) activation. In the present study, we investigated the effects of dexamethasone on SCF-induced migration of rat peritoneal mast cells (RPMCs). SCF significantly induced migration of RPMCs at 4 h. Dexamethasone dose-dependently inhibited SCF-induced migration of RPMCs (about 90.1% at 100 nM, P<0.05). MAPK p38 inhibitor, SB203580 (20 ${\mu}$M) also inhibited the SCF-induced migration. The ability of SCF to enhance morphological alteration and F -actin formation was also abolished by treatment of dexamethasone. Dexamethasone inhibited SCF-induced p38 MAPK activation to near basal level and induced the MKP-1 expression. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment of dexamethasone or SB203580 (p<0.01). Our results show that dexamethasone potently regulates SCF -induced migration, p38 MAPK activation and inflammatory cytokine production through expression of MKP-l protein in RPMCs. Such modulation may have functional consequences during dexamethasone treatment, especially mast cell-mediated allergic inflammation disorders.

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