4.5 Article

Evaluation of a Streptococcus thermophilus strain with innate anti-inflammatory properties as a vehicle for IL-10 cDNA delivery in an acute colitis model

Journal

CYTOKINE
Volume 73, Issue 2, Pages 177-183

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2015.02.020

Keywords

Inflammatory bowel disease; Streptococcus thermophilus; DNA delivery; Interleukin-10; Anti-inflammatory

Funding

  1. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
  2. Centro Brasileiro-Argentino de Biotecnologia (CBAB-CABBIO)
  3. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
  4. Consejo Nacional de lnvestigaciones Cientificas y Tecnicas (CONICET)
  5. Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT)

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The aim of this work was to develop a Streptococcus (S.) thermophilus strain with improved anti-inflammatory properties due to the incorporation of the therapeutic cDNA delivery plasmid pValac::il-10. To achieve this purpose, cells of S. thermophilus CRL807, previously selected as being an important anti-inflammatory strain, were electroporated with pValac::i1-10 plasmid. In order to confirm the functionality of the developed strain, it was co-cultured with human epithelial cells Caco-2 and the production of IL-10 was evaluated by ELISA. Bacterial suspensions of S. thermophilus CRL807 containing pValac::i1-10 plasmid or of the wild-type (WT) strain were administered in vivo using a murine model of intestinal inflammation. The animals treated with S. thermophilus CRL807 pValac::i1-10 showed a lower body weight loss, microbial translocation to liver and damage scores in their intestines at macroscopical and microscopic levels. Furthermore, a significant increase was observed in the concentration of IL-10 in the intestinal contents of these mice compared to the rest of the experimental groups, accompanied by decreased levels of pro-inflammatory cytokines. The insertion of the therapeutic pValac::i1-10 plasmid increased the intrinsic anti-inflammatory activity (synergetic effect) of S. thermophilus CRL807 which could be included in novel treatment protocols for inflammatory bowel diseases. (C) 2015 Elsevier Ltd. All rights reserved.

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