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

• Published in: Endocrinology (Philadelphia) 2003-09, Vol.144 (9), p.4080-4086
• Main Authors: Jeong, Hyun-Ja, Na, Ho-Jeong, Hong, Seung-Heon, Kim, Hyung-Min
• Format: Article
• Language: English
• Subjects: Actin; Actins - drug effects; Actins - metabolism; Animals; Bioaccumulation; Biological and medical sciences; Cell activation; Cell Cycle Proteins; Cell migration; Cell Movement - drug effects; Cell number; Cells, Cultured; Cytokines; Dexamethasone; Dexamethasone - pharmacology; Dual Specificity Phosphatase 1; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Glucocorticoids; Glucocorticoids - pharmacology; Hypersensitivity; Imidazoles - pharmacology; Immediate-Early Proteins - metabolism; In Vitro Techniques; Inflammation; Interleukin-6 - biosynthesis; Male; MAP kinase; MAP kinase phosphatase; Mast cells; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - metabolism; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; MKP-1 protein; p38 Mitogen-Activated Protein Kinases; Peritoneum - cytology; Phosphoprotein Phosphatases; Protein Phosphatase 1; Protein Tyrosine Phosphatases - metabolism; Pyridines - pharmacology; Rats; Rats, Wistar; Stem cell factor; Stem Cell Factor - metabolism; Stem cells; Tumor Necrosis Factor-alpha - biosynthesis; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2003-0115

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.