The COX-2 inhibitor SC-236 exerts anti-inflammatory effects by suppressing phosphorylation of ERK in a murine model

• Published in: Life sciences (1973) 2007-08, Vol.81 (11), p.863-872
• Main Authors: Kim, Su-Jin, Jeong, Hyun-Ja, Moon, Phil-Dong, Myung, Noh-Yil, Kim, Min-Cheol, Kang, Tae-Hee, Lee, Kang-Min, Park, Rae-Kil, So, Hong-seob, Kim, Eun-Cheol, An, Nyeon-Hyoung, Um, Jae-Young, Kim, Hyung-Min, Hong, Seung-Heon
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; COX-2 inhibitor; Cyclooxygenase Inhibitors - pharmacology; Dinoprostone - metabolism; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases - metabolism; Extracellular signal-regulated protein kinase; Histamine - metabolism; Immunoglobulin E - chemistry; Inflammatory allergic reaction; Interleukin-6 - metabolism; Mice; NF-kappa B - metabolism; Passive cutaneous anaphylaxis; Phosphorylation; Pyrazoles - pharmacology; Rats; Sulfonamides - pharmacology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2007.06.027

SC-236, (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-]benzenesulfonamide; C 16H 11ClF 3N 3O 2S) 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)-α. 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.