Low-dose plasmid DNA treatment increases plasma vasopressin and regulates blood pressure in experimental endotoxemia

Autor(es)

Malardo, Thiago ^[1] ; Batalhao, Marcelo E. ^[2] ; Panunto-Castelo, Ademilson ^[3] ; Almeida, Luciana P. ^[1] ; Padilha, Everton ^[1] ; Fontoura, Isabela C. ^[1] ; Silva, Celio L. ^[1] ; Carnio, Evelin C. ^[2] ; Coelho-Castelo, Arlete A. M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Biochem & Immunol, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Gen & Specialized Nursing, Coll Nursing Ribeirao Preto, BR-14040902 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dept Biol, Sch Philosophy Sci & Literature Ribeirao Preto, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC IMMUNOLOGY; v. 13, NOV 8 2012.
• Citações Web of Science: 1

Resumo

Background: Although plasmid DNA encoding an antigen from pathogens or tumor cells has been widely studied as vaccine, the use of plasmid vector (without insert) as therapeutic agent requires further investigation. Results: Here, we showed that plasmid DNA (pcDNA3) at low doses inhibits the production of IL-6 and TNF-alpha by lipopolysaccharide (LPS)-stimulated macrophage cell line J774. These findings led us to evaluate whether plasmid DNA could act as an anti-inflammatory agent in a Wistar rat endotoxemia model. Rats injected simultaneously with 1.5 mg/kg of LPS and 10 or 20 mu g of plasmid DNA had a remarkable attenuation of mean arterial blood pressure (MAP) drop at 2 hours after treatment when compared with rats injected with LPS only. The beneficial effect of the plasmid DNA on MAP was associated with decreased expression of IL-6 in liver and increased concentration of plasma vasopressin (AVP), a known vasoconstrictor that has been investigated in hemorrhagic shock management. No difference was observed in relation to nitric oxide (NO) production. Conclusion: Our results demonstrate for the first time that plasmid DNA vector at low doses presents anti-inflammatory property and constitutes a novel approach with therapeutic potential in inflammatory diseases. (AU)

• Processo FAPESP: 06/03987-7 - Uso de rna mensageiro como nova abordagem em terapia genica ou modelos vacinais contra tuberculose.
• Beneficiário: Arlete Aparecida Martins Coelho-Castelo
• Modalidade de apoio: Auxílio à Pesquisa - Regular