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

Life Sci. 2007 Aug 23;81(11):863-72. doi: 10.1016/j.lfs.2007.06.027. Epub 2007 Sep 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Histamine / metabolism
  • Immunoglobulin E / chemistry
  • Interleukin-6 / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Phosphorylation
  • Pyrazoles / pharmacology*
  • Rats
  • Sulfonamides / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide
  • Anti-Inflammatory Agents
  • Cyclooxygenase Inhibitors
  • Interleukin-6
  • NF-kappa B
  • Pyrazoles
  • Sulfonamides
  • Tumor Necrosis Factor-alpha
  • Immunoglobulin E
  • Histamine
  • Extracellular Signal-Regulated MAP Kinases
  • Dinoprostone