[Therapeutic effect of the low molecular weight inhibitor of the NF-kappaB signaling pathway on experimental autoimmune uveoretinitis].

Abstract

The nuclear factor-kappaB (NF-kappaB) proteins are a family of ubiquitously expressed transcriptional proteins in most immune and inflammatory responses. Understanding the precise regulation of the NF-kappaB family can lead to the development of effective new drugs for the treatment of autoimmune and inflammatory disorders. STA-5326 is a low molecular weight compound developed through highthroughput IL-12/ IL-23 p40 inhibitor screening. STA-5326 suppresses IL-12/23 p40 production through suppression of the NF-kappaB family (c-Rel) nuclear accumulation. Experimental autoimmune uveoretinitis (EAU) is an animal model that shares many clinical and histological features with human uveitic disorders. In the current study, we investigated whether oral administration of STA-5326 is effective in influencing experimental autoimmune uveoretinitis (EAU). Clinical and histopathological analysis of our results show that oral administration of STA-5326 during the entire phase reduced the severity of EAU. Furthermore, oral administration of STA-5326 during the effector phase of EAU ameliorated the severity of inflammation. Furthermore, the serum levels of IL-12/23 p40 significantly decreased in STA-5326 treated mice. These results indicate that oral administration of STA-5326 is effective in suppressing inflammation in the EAU model. The new NF-kappaB inhibitor, STA-5326 represents a promising therapeutic modality for refractory uveitis in humans.

• Authors: Hiroshi Keino
• Journal: Nippon Ganka Gakkai zasshi (Nippon Ganka Gakkai Zasshi) Vol. 114 Issue 11 Pg. 944-54 (Nov 2010) ISSN: 0029-0203 [Print] Japan
• PMID: 21141074 (Publication Type: Journal Article, Review)

Chemical References

• Hydrazones
• Morpholines
• NF-kappa B
• Pyrimidines
• Triazines
• apilimod

Topics

• Animals
• Autoimmune Diseases
• Hydrazones
• Mice
• Morpholines (therapeutic use)
• NF-kappa B (antagonists & inhibitors)
• Pyrimidines
• Retinitis (drug therapy)
• Signal Transduction
• Triazines (therapeutic use)
• Uveitis (drug therapy)