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de Araújo Junqueira, Ana Flávia Torquato; Dias, Adriana Abalen Martins; Vale, Mariana Lima; Spilborghs, Graziela Machado Gruner Turco; Bossa, Aline Siqueira; Lima, Bruno Bezerra; Carvalho, Alex Fiorini; Guerrant, Richard Littleton; Ribeiro, Ronaldo Albuquerque; Brito, Gerly Anne

Adenosine Deaminase Inhibition PreventsClostridium difficileToxin A-Induced Enteritis in Mice

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  • Media type: E-Article
  • Title: Adenosine Deaminase Inhibition PreventsClostridium difficileToxin A-Induced Enteritis in Mice
  • Contributor: de Araújo Junqueira, Ana Flávia Torquato; Dias, Adriana Abalen Martins; Vale, Mariana Lima; Spilborghs, Graziela Machado Gruner Turco; Bossa, Aline Siqueira; Lima, Bruno Bezerra; Carvalho, Alex Fiorini; Guerrant, Richard Littleton; Ribeiro, Ronaldo Albuquerque; Brito, Gerly Anne
  • imprint: American Society for Microbiology, 2011
  • Published in: Infection and Immunity
  • Language: English
  • DOI: 10.1128/iai.01159-10
  • ISSN: 0019-9567; 1098-5522
  • Keywords: Infectious Diseases ; Immunology ; Microbiology ; Parasitology
  • Origination:
  • Footnote:
  • Description: <jats:title>ABSTRACT</jats:title><jats:p>Toxin A (TxA) is able to induce most of the classical features of<jats:italic>Clostridium difficile</jats:italic>-associated disease in animal models. The objective of this study was to determine the effect of an inhibitor of adenosine deaminase, EHNA [erythro-9-(2-hydroxy-3-nonyl)-adenine], on TxA-induced enteritis in C57BL6 mice and on the gene expression of adenosine receptors. EHNA (90 μmol/kg) or phosphate-buffered saline (PBS) was injected intraperitoneally (i.p.) 30 min prior to TxA (50 μg) or PBS injection into the ileal loop. A<jats:sub>2A</jats:sub>adenosine receptor agonist (ATL313; 5 nM) was injected in the ileal loop immediately before TxA (50 μg) in mice pretreated with EHNA. The animals were euthanized 3 h later. The changes in the tissue were assessed by the evaluation of ileal loop weight/length and secretion volume/length ratios, histological analysis, myeloperoxidase assay (MPO), the local expression of inducible nitric oxide synthase (NOS2), pentraxin 3 (PTX3), NF-κB, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) by immunohistochemistry and/or quantitative reverse transcription-PCR (qRT-PCR). The gene expression profiles of A<jats:sub>1</jats:sub>, A<jats:sub>2A</jats:sub>, A<jats:sub>2B</jats:sub>, and A<jats:sub>3</jats:sub>adenosine receptors also were evaluated by qRT-PCR. Adenosine deaminase inhibition, by EHNA, reduced tissue injury, neutrophil infiltration, and the levels of proinflammatory cytokines (TNF-α and IL-1β) as well as the expression of NOS2, NF-κB, and PTX3 in the ileum of mice injected with TxA. ATL313 had no additional effect on EHNA action. TxA increased the gene expression of A<jats:sub>1</jats:sub>and A<jats:sub>2A</jats:sub>adenosine receptors. Our findings show that the inhibition of adenosine deaminase by EHNA can prevent<jats:italic>Clostridium difficile</jats:italic>TxA-induced damage and inflammation possibly through the A<jats:sub>2A</jats:sub>adenosine receptor, suggesting that the modulation of adenosine/adenosine deaminase represents an important tool in the management of<jats:italic>C. difficile-</jats:italic>induced disease.</jats:p>
  • Access State: Open Access