The regulatory effect of SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l]benzenesulfonamide) on stem cell factor induced migration of mast cells.
SC-236, (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-]benzenesulfonamide; C(16)H(11)ClF(3)N(3)O(2)S), is a highly selective cyclooxygenase (COX)-2 inhibitor. Recently, there have been reports that SC-236 protects against cartilage damage in addition to reducing inflammation and pain in osteoarthritis. However, the mechanism involved in the inflammatory allergic reaction has not been examined. Mast cells accumulation can be related to inflammatory conditions, including allergic rhinitis, asthma, and rheumatoid arthritis. The aim of the present study is to investigate the effects of SC-236 on stem cell factor (SCF)-induced migration, morphological alteration, and cytokine production of rat peritoneal mast cells (RPMCs). We observed that SCF significantly induced the migration and morphological alteration. The ability of SCF to enhance migration and morphological alteration was abolished by treatment with SC-236. In addition, production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and vascular endothelial growth factor (VEGF) production induced by SCF was significantly inhibited by treatment with SC-236. Previous work has demonstrated that SCF-induced migration and cytokine production of mast cells require p38 MAPK activation. We also showed that SC-236 suppresses the SCF-induced p38 MAPK activation in RPMCs. These data suggest that SC-236 inhibits migration and cytokine production through suppression of p38 MAPK activation. These results provided new insight into the pharmacological actions of SC-236 and its potential therapeutic role in the treatment of inflammatory allergic diseases.
Kim
Su-Jin
SJ
VestibuloCochlear Research Center of Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
Jeong
Hyun-Ja
HJ
Park
Rae-Kil
RK
Lee
Kang-Min
KM
Kim
Hyung-Min
HM
Um
Jae-Young
JY
Hong
Seung-Heon
SH
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010529:Peritoneal Cavity / Q000166:cytology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000096926:Benzenesulfonamides
D000199:Actins; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D053583:Interleukin-1beta; D011720:Pyrazoles; D019089:Stem Cell Factor; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D048051:p38 Mitogen-Activated Protein Kinases; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides