title: Amelioration of experimental autoimmune encephalomyelitis by plumbagin through down-regulation of JAK-STAT and NF-κB signaling pathways.
abstract: Plumbagin (PL), a herbal compound derived from roots of the medicinal plant Plumbago zeylanica, has been shown to have immunosuppressive properties. Present report describes that PL is a potent novel agent in control of encephalitogenic T cell responses and amelioration of mouse experimental autoimmune encephalomyelitis (EAE), through down-regulation of JAK-STAT pathway. PL was found to selectively inhibit IFN-γ and IL-17 production by CD4(+) T cells, which was mediated through abrogated phosphorylation of JAK1 and JAK2. Consistent with IFN-γ and IL-17 reduction was suppressed STAT1/STAT4/T-bet pathway which is critical for Th1 differentiation, as well as STAT3/ROR pathway which is essential for Th17 differentiation. In addition, PL suppressed pro-inflammatory molecules such as iNOS, IFN-γ and IL-6, accompanied by inhibition of IκB degradation as well as NF-κB phosphorylation. These data give new insight into the novel immune regulatory mechanism of PL and highlight the great value of this kind of herb compounds in probing the complex cytokine signaling network and novel therapeutic targets for autoimmune diseases.
authors: Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors: Yan
authors: Y
authors: Jia
authors: Ji
authors: J
authors: Jing
authors: Yang
authors: Y
authors: Bai
authors: Zhen
authors: Z
authors: Li
authors: Lande
authors: L
authors: Liu
authors: Jian
authors: J
authors: Luo
authors: Mingyao
authors: M
authors: Liu
authors: Huaqing
authors: H
authors: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D016328:NF-kappa B / Q000378:metabolism*; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C571327:Mog protein, mouse; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D016328:NF-kappa B; D009285:Naphthoquinones; D050791:STAT Transcription Factors; D053612:Janus Kinases; C014758:plumbagin