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: Mario J Bibolini, M Julia Scerbo, Nahuel Peinetti, German A Roth, Clara G Monferran
• Journal: Cellular immunology (Cell Immunol) Vol. 280 Issue 1 Pg. 50-60 (Nov 2012) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 23261829 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Bacterial Toxins
• Enterotoxins
• Escherichia coli Proteins
• Lymphokines
• Myelin Basic Protein
• Peptide Fragments
• Recombinant Fusion Proteins
• Synapsins
• G(M1) Ganglioside
• heat-labile enterotoxin, E coli

Topics

• Animals
• Bacterial Toxins (chemistry, genetics, therapeutic use)
• CHO Cells (drug effects, metabolism)
• Cattle
• Cricetinae
• Drug Evaluation, Preclinical
• Encephalomyelitis, Autoimmune, Experimental (drug therapy)
• Endocytosis
• Enterotoxins (chemistry, genetics, therapeutic use)
• Escherichia coli Proteins (chemistry, genetics, therapeutic use)
• Female
• G(M1) Ganglioside (metabolism)
• Lymphocyte Activation (drug effects)
• Lymphokines (metabolism)
• Male
• Myelin Basic Protein (immunology, toxicity)
• Peptide Fragments (chemistry, therapeutic use)
• Protein Denaturation
• Protein Folding
• Protein Structure, Tertiary
• Random Allocation
• Rats
• Rats, Wistar
• Recombinant Fusion Proteins (chemistry, therapeutic use)
• Single-Blind Method
• Structure-Activity Relationship
• Synapsins (chemistry, genetics, therapeutic use)
• T-Lymphocytes, Regulatory (drug effects, immunology)