HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

A fumigaclavine C isostere alleviates Th1-mediated experimental colitis via competing with IFN-γ for binding to IFN-γ receptor 1.

Abstract
Interferon gamma (IFN-γ) signaling in T cells plays an important role in developing T helper 1 (Th1)-mediated inflammation. Selective regulation of IFN-γ signaling is an attractive strategy for treating Th1-mediated immune diseases. In this study, we aimed to explore possible means of targeting IFN-γ signaling by using small molecule compound. A synthetic small molecule FC9 was identified as it selectively inhibited IFN-γ signaling in T cells without suppressing interleukin 4 (IL-4) signaling. Furthermore, FC9 inhibited IFN-γ-induced Janus kinase 2 (JAK2) activation via competing with IFN-γ for binding to IFN-γ receptor 1 (IFN-γ R1). Interestingly, we found that FC9 bound to IFN-γ R1 and selectively suppressed Th1 but not Th2 immune response in T cells, resulting in an improvement in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. In conclusion, FC9-induced competitive blockade of IFN-γ R1 for selective inhibition of IFN-γ signaling, demonstrated a novel mean of targeting IFN-γ signaling. These findings could lead to increased options for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases.
AuthorsYang Tan, Xingxin Wu, Jing Sun, Wenjie Guo, Fangyuan Gong, Fenli Shao, Tao Tan, Yi Cao, Bingfeng Zheng, Yanhong Gu, Yang Sun, Qiang Xu
JournalBiochemical pharmacology (Biochem Pharmacol) Vol. 123 Pg. 63-72 (Jan 01 2017) ISSN: 1873-2968 [Electronic] England
PMID27751819 (Publication Type: Journal Article)
CopyrightCopyright © 2016 Elsevier Inc. All rights reserved.
Chemical References
  • Ergot Alkaloids
  • Indole Alkaloids
  • Receptors, Interferon
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • fumigaclavine C
  • interferon gamma receptor
  • Interferon-gamma
Topics
  • Animals
  • Cell Differentiation
  • Colitis (immunology, prevention & control)
  • Ergot Alkaloids (pharmacology)
  • Indole Alkaloids (pharmacology)
  • Interferon-gamma (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Interferon (metabolism)
  • STAT1 Transcription Factor (metabolism)
  • Signal Transduction
  • Th1 Cells (cytology, immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: