title: Inhibition of the stem cell factor-induced migration of mast cells by dexamethasone.
abstract: 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 (approximately 90.1% at 100 nM; P < 0.05). The MAPK p38 inhibitor SB203580 (20 microM) 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.
authors.affiliation: Department of Pharmacology, Kyung Hee University College of Oriental Medicine, 130-701 Seoul, South Korea.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Ho-Jeong
authors.initials: HJ
authors.lastname: Na
authors.forename: Seung-Heon
authors.initials: SH
authors.lastname: Hong
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010537:Peritoneum / Q000166:cytology; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019089:Stem Cell Factor / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000199:Actins; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007093:Imidazoles; D017874:Immediate-Early Proteins; D015850:Interleukin-6; D011725:Pyridines; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases; C093642:SB 203580