title: The hybrid between the ABC domains of synapsin and the B subunit of Escherichia coli heat-labile toxin ameliorates experimental autoimmune encephalomyelitis.
abstract: The B subunit of Escherichia coli heat-labile enterotoxin (LTB) acts as efficient mucosal carrier for conjugated antigens. We expressed two heterologous proteins using E. coli as a host: a hybrid consisting of LTB and the A, B and C domain of synapsin (LTBABC) and the separated ABC peptide of this synaptic protein. Refolded LTBABC and LTB bound to the GM1 receptor and internalized into CHO-K1(GM1+) cells. LTBABC showed enhanced solubility and cell binding ability respect to the former hybrid LTBSC. Several oral doses of LTBABC were administered to rats with experimental autoimmune encephalomyelitis (EAE) from induction to the acute stage of the disease. This treatment decreased disease severity, delayed type hypersensitivity reaction and lymph node cell proliferation stimulated by myelin basic protein. Amelioration of EAE was also associated with modulation of the Th1/Th2 cytokine ratio, increased TGF-β secretion in mesenteric lymph nodes as well as expansion of CD4(+)CD25(+)Foxp3(+) regulatory T cell population. These results indicate that the fusion protein LTBABC is suitable for further exploration of its therapeutic effect on EAE development.
authors.affiliation: Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC, UNC-CONICET), Departamento de Química Biológica, Universidad Nacional de Córdoba. Haya de la Torre y Medina Allende, Ciudad Universitaria, Córdoba, Argentina.
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Bibolini
authors.forename: M
authors.initials: M
authors.lastname: Julia Scerbo
authors.forename: Nahuel
authors.initials: N
authors.lastname: Peinetti
authors.forename: German A
authors.initials: GA
authors.lastname: Roth
authors.forename: Clara G
authors.initials: CG
authors.lastname: Monferran
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D004705:Endocytosis; D004768:Enterotoxins / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D005260:Female; D005677:G(M1) Ganglioside / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology / Q000633:toxicity; D010446:Peptide Fragments / Q000737:chemistry / Q000627:therapeutic use; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000627:therapeutic use; D016037:Single-Blind Method; D013329:Structure-Activity Relationship; D016704:Synapsins / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D008222:Lymphokines; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D016704:Synapsins; D005677:G(M1) Ganglioside; C027538:heat-labile enterotoxin, E coli