The hybrid between the ABC domains of synapsin and the B subunit of Escherichia coli heat-labile toxin ameliorates experimental autoimmune encephalomyelitis
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-beta 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. (C) 2012 Elsevier Inc. All rights reserved.
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IPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, MexicoIPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, Mexico
Martinez-Gonzalez, Luzmila
Rosales-Mendoza, Sergio
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IPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, MexicoIPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, Mexico
Rosales-Mendoza, Sergio
Soria-Guerra, Ruth Elena
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IPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, MexicoIPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, Mexico
Soria-Guerra, Ruth Elena
Moreno-Fierros, Leticia
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Univ Nacl Autonoma Mexico, UBIMED, FES Iztacala, Los Reyes Iztacala 54090, Tlalnepantla, MexicoIPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, Mexico
Moreno-Fierros, Leticia
Lopez-Revilla, Ruben
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IPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, MexicoIPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, Mexico
Lopez-Revilla, Ruben
Korban, Schuyler S.
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Univ Illinois, Dept Nat Resources & Environm Sci, Urbana, IL 61801 USAIPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, Mexico
Korban, Schuyler S.
Guevara-Arauza, Juan C.
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Univ Autonoma San Luis Potosi, Fac Ciencias Quim, Lab Biofarmaceut Recombinantes, San Luis Potosi 78210, SLP, MexicoIPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, Mexico
Guevara-Arauza, Juan C.
Alpuche-Solis, Angel Gabriel
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IPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, MexicoIPICYT, Div Biol Mol, San Luis Potosi 78216, SLP, Mexico