title: Immunomodulatory effects and improved prognosis of experimental autoimmune encephalomyelitis after O-tetradecanoyl-genistein treatment.
abstract: Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis (MS), a human inflammatory demyelinating disease of the central nervous system. Genistein, an isoflavonoid phytoestrogenic compound found in soy, is known to reverse clinical signs of EAE. Although genistein has some potential in clinical application, it has some disadvantages related to its chemical structure, such as rapid in vivo metabolism and a fast decline in serum after oral administration. The present work investigates the treatment of EAE by using 7-O-tetradecanoyl-genistein (TDG), a more lipophilic analog of genistein obtained by esterification. The clinical course of EAE was investigated in C57Bl/6 mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG)(35-55) in complete Freund's adjuvant supplemented with Mycobacterium tuberculosis H37RA. After 14 days of MOG immunization, mice were treated with TDG for seven days. Numbers of IL-17-producing cells and Foxp3 by CD4(+) T cells and CTLA-4 expression by CD3(+) T cells from brain were determined by flow cytometry. Levels of IL-6, IFN-γ and IL-10 were evaluated by ELISA. Brain sections were stained by hematoxylin and eosin method. The data obtained indicate that TDG treatment ameliorates the clinical signs of EAE, which correlates with a decrease of IL-17-producing cells and an increase in Foxp3(+)CD4(+) cells in the brain. TDG is also shown to enhance IL-10 production and CTLA-4 expression and to reduce IFN-γ and IL-6. Altogether, these findings suggest an immunomodulatory therapeutic role for TDG in EAE and multiple sclerosis.
authors.affiliation: Department of Parasitology, Microbiology and Immunology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
authors.forename: Sandra B R
authors.initials: SB
authors.lastname: Castro
authors.forename: Celso O R
authors.initials: CO
authors.lastname: Junior
authors.forename: Caio C S
authors.initials: CC
authors.lastname: Alves
authors.forename: Alyria T
authors.initials: AT
authors.lastname: Dias
authors.forename: Lívia L
authors.initials: LL
authors.lastname: Alves
authors.forename: Luciano
authors.initials: L
authors.lastname: Mazzoccoli
authors.forename: Felipe P
authors.initials: FP
authors.lastname: Mesquita
authors.forename: Nathália S V
authors.initials: NS
authors.lastname: Figueiredo
authors.forename: Maria A
authors.initials: MA
authors.lastname: Juliano
authors.forename: Maria Christina M N
authors.initials: MC
authors.lastname: Castañon
authors.forename: Jacy
authors.initials: J
authors.lastname: Gameiro
authors.forename: Mauro V
authors.initials: MV
authors.lastname: Almeida
authors.forename: Henrique C
authors.initials: HC
authors.lastname: Teixeira
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ferreira
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D005620:Freund's Adjuvant / Q000276:immunology; D019833:Genistein / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology*; D007155:Immunologic Factors / Q000276:immunology* / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009185:Myelin Proteins / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein
chemical_list: D000276:Adjuvants, Immunologic; D017252:CD3 Complex; D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007155:Immunologic Factors; D007378:Interleukins; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D007371:Interferon-gamma; D005620:Freund's Adjuvant; D019833:Genistein