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Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes.
J Immunol 2002; 168(12):6506-13JI

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.

Authors+Show Affiliations

Division of Neuroimmunology, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12055272

Citation

Natarajan, Chandramohan, and John J. Bright. "Curcumin Inhibits Experimental Allergic Encephalomyelitis By Blocking IL-12 Signaling Through Janus kinase-STAT Pathway in T Lymphocytes." Journal of Immunology (Baltimore, Md. : 1950), vol. 168, no. 12, 2002, pp. 6506-13.
Natarajan C, Bright JJ. Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. J Immunol. 2002;168(12):6506-13.
Natarajan, C., & Bright, J. J. (2002). Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. Journal of Immunology (Baltimore, Md. : 1950), 168(12), pp. 6506-13.
Natarajan C, Bright JJ. Curcumin Inhibits Experimental Allergic Encephalomyelitis By Blocking IL-12 Signaling Through Janus kinase-STAT Pathway in T Lymphocytes. J Immunol. 2002 Jun 15;168(12):6506-13. PubMed PMID: 12055272.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. AU - Natarajan,Chandramohan, AU - Bright,John J, PY - 2002/6/11/pubmed PY - 2002/7/18/medline PY - 2002/6/11/entrez SP - 6506 EP - 13 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 168 IS - 12 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/12055272/Curcumin_inhibits_experimental_allergic_encephalomyelitis_by_blocking_IL_12_signaling_through_Janus_kinase_STAT_pathway_in_T_lymphocytes_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=12055272 DB - PRIME DP - Unbound Medicine ER -