The COX-2 inhibitor SC-236 exerts anti-inflammatory effects by suppressing phosphorylation of ERK in a murine model.
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 for those with osteoarthritis. However, the mechanism involved in an inflammatory allergic reaction in a murine model has not been examined. The aim of the present study is to elucidate whether and how SC-236 modulates the inflammatory allergic reaction in a murine model. In this study, the anti-allergic effect was investigated using rat peritoneal mast cells, IgE-induced passive cutaneous anaphylaxis (PCA), and the ear-swelling model in mice. Also, we examined the inhibitory effect of SC-236 on the expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha. SC-236 was found to inhibit the ear-swelling response and histamine release in the murine model. Additionally, SC-236 was revealed to inhibit the PCA response and COX-2 expression. As a final step, the inhibitory mechanism of SC-236 was shown to occur through phosphorylation of extracellular signal-regulated protein kinase (ERK). These in vitro and in vivo results provide new insight into the pharmacological actions of SC-236 as a potential molecule for therapy for inflammatory allergic diseases.
Kim
Su-Jin
SJ
College of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul, 130-701, Republic of Korea.
Jeong
Hyun-Ja
HJ
Moon
Phil-Dong
PD
Myung
Noh-Yil
NY
Kim
Min-Cheol
MC
Kang
Tae-Hee
TH
Lee
Kang-Min
KM
Park
Rae-Kil
RK
So
Hong-seob
HS
Kim
Eun-Cheol
EC
An
Nyeon-Hyoung
NH
Um
Jae-Young
JY
Kim
Hyung-Min
HM
Hong
Seung-Heon
SH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism; D007073:Immunoglobulin E / Q000737:chemistry; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000096926:Benzenesulfonamides