Inhibition of the stem cell factor-induced migration of mast cells by dexamethasone.
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.
Jeong
Hyun-Ja
HJ
Department of Pharmacology, Kyung Hee University College of Oriental Medicine, 130-701 Seoul, South Korea.
Na
Ho-Jeong
HJ
Hong
Seung-Heon
SH
Kim
Hyung-Min
HM
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
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