title: Protective effect of a synapsin peptide genetically fused to the B subunit of Escherichia coli heat-labile enterotoxin in rat autoimmune encephalomyelitis.
abstract: Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease with similarities to multiple sclerosis that requires the activation of auto reactive T cells that infiltrate the central nervous system. In previous studies we have shown that intraperitoneal administration of synaptosomal antigens could suppress EAE. Herein we examined the effect in this animal model of a fusion protein comprising the C domain of synapsin Ia and the B subunit of Escherichia coli heat-labile enterotoxin (LTBSC). Oral administration to rats of low amounts of LTBSC induced immunological systemic tolerance to the encephalitogenic myelin basic protein. Treatment with LTBSC prior to EAE induction diminished disease incidence, DTH reaction to myelin basic protein, and central nervous system inflammation. LTBSC treatment also reduced the specific T-cell proliferative response to myelin basic protein, decreased nitric oxide production, and augmented arginase activity by peritoneal macrophages. All animals challenged for EAE developed antibody response specific for myelin basic protein, but rats treated with LTBSC showed a lower IgG2b/IgG1 ratio, indicating a shift to a Th2-type milieu. The data presented here suggest that well-conserved synapsin peptides conjugated to the B subunit of enterotoxins from the cholera toxin family have a protective role and provide a potential therapeutic tool for intervention in EAE as well as in multiple sclerosis.
authors.affiliation: Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC, UNC-CONICET), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: M Julia
authors.initials: MJ
authors.lastname: Scerbo
authors.forename: Lucia L
authors.initials: LL
authors.lastname: Rupil
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Bibolini
authors.forename: German A
authors.initials: GA
authors.lastname: Roth
authors.forename: Clara G
authors.initials: CG
authors.lastname: Monferran
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D004768:Enterotoxins / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000473:pathology; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology*; D016704:Synapsins / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D004676:Myelin Basic Protein; D010455:Peptides; D011993:Recombinant Fusion Proteins; D016704:Synapsins; C027538:heat-labile enterotoxin, E coli