Curcumin Inhibits Experimental Allergic Encephalomyelitis by Blocking IL-12 Signaling Through Janus Kinase-STAT Pathway in T Lymphocytes
Open Access
- 15 June 2002
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 168 (12), 6506-6513
- https://doi.org/10.4049/jimmunol.168.12.6506
Abstract
Experimental allergic encephalomyelitis (EAE) is a CD4+ Th1 cell-mediated inflammatory demyelinating autoimmune disease of the CNS that serves as an animal model for multiple sclerosis (MS). IL-12 is a proinflammatory cytokine that plays a crucial role in the induction of neural Ag-specific Th1 differentiation and pathogenesis of CNS demyelination in EAE and MS. Curcumin (1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a naturally occurring polyphenolic phytochemical isolated from the rhizome of the medicinal plant Curcuma longa. It has profound anti-inflammatory activity and been traditionally used to treat inflammatory disorders. In this study we have examined the effect and mechanism of action of curcumin on the pathogenesis of CNS demyelination in EAE. In vivo treatment of SJL/J mice with curcumin significantly reduced the duration and clinical severity of active immunization and adoptive transfer EAE. Curcumin inhibited EAE in association with a decrease in IL-12 production from macrophage/microglial cells and differentiation of neural Ag-specific Th1 cells. In vitro treatment of activated T cells with curcumin inhibited IL-12-induced tyrosine phosphorylation of Janus kinase 2, tyrosine kinase 2, and STAT3 and STAT4 transcription factors. The inhibition of Janus kinase-STAT pathway by curcumin resulted in a decrease in IL-12-induced T cell proliferation and Th1 differentiation. These findings highlight the fact that curcumin inhibits EAE by blocking IL-12 signaling in T cells and suggest its use in the treatment of MS and other Th1 cell-mediated inflammatory diseases.Keywords
This publication has 56 references indexed in Scilit:
- Immunomodulatory drugs for multiple sclerosis: a systematic review of clinical and cost effectivenessExpert Opinion on Pharmacotherapy, 2001
- Molecular mechanisms of NF-κB activation induced by bacterial lipopolysaccharide through Toll-like receptorsInnate Immunity, 2000
- IL-12 enhances IL-2 function by inducing CD25 expression through a p38 mitogen-activated protein kinase pathwayEuropean Journal of Immunology, 2000
- Interferon β in multiple sclerosis: is IL-12 suppression the key?Immunology Today, 2000
- The role of IL-12 in the induction of organ-specific autoimmune diseasesImmunology Today, 1995
- Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4.The Journal of Experimental Medicine, 1995
- Curcumin, an Anti-tumor Promoter and Anti-inflammatory Agent, Inhibits Induction of Nitric Oxide Synthase in Activated MacrophagesBiochemical and Biophysical Research Communications, 1995
- Three Non-Phenolic Diarylheptanoids with Anti-Inflammatory Activity fromCurcuma xanthorrhizaPlanta Medica, 1993
- Immunological Aspects of Demyelinating DiseasesAnnual Review of Immunology, 1992
- Anti-inflammatory and irritant activities of curcumin analogues in ratsInflammation Research, 1982