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

Department of Pharmacology, Kyung Hee University College of Oriental Medicine (H.-J.J., H.-J.N., H.-M.K.), 130-701 Seoul, South Korea; and College of Pharmacy, VestibuloCochlear Research Center of Wonkwang University (H.-J.J., H.-J.N., S.-H.H.), 570-749 Jeonbuk, South Korea

Address all correspondence and requests for reprints to: Dr. Hyung-Min Kim, Department of Pharmacology, Kyung Hee University College of Oriental Medicine, 1 Hoegi-Dong, Dongdaemun-Gu, 130-701 Seoul, South Korea. E-mail: hmkim{at}khu.ac.kr.

Mast cell accumulation can be causally related to 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 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 the migration of RPMCs at 4 h. Dexamethasone dose-dependently inhibited SCF-induced migration of RPMCs (90.1% at 100 nM; P < 0.05). The MAPK p38 inhibitor SB203580 (20 µM) also inhibited the SCF-induced migration. The ability of SCF to enhance morphological alteration and filamentous actin formation was also abolished by treatment with dexamethasone. Dexamethasone inhibited SCF-induced p38 MAPK activation to near-basal levels and induced MAPK phosphatase-1 expression. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment with dexamethasone or SB203580 (P < 0.01). Our results show that dexamethasone potently regulates SCF-induced migration, p38 MAPK activation, and inflammatory cytokine production through the expression of MKP-1 protein in RPMCs. Such modulation may have functional consequences during dexamethasone treatment, especially mast cell-mediated allergic inflammation disorders.

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