| Role of TNF-α in the Mechanisms Responsible for Preterm Delivery Induced by Stx2 in Rats. | |
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MedLine Citation:
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PMID: 23043728 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE.: Shiga toxin-producing Escherichia coli (STEC) infections could be one of the causes of fetal morbimortality in pregnant women. We have previously reported that Shiga toxin type 2 (Stx2) causes preterm delivery in pregnant rats. In this study, we evaluate the role of tumor necrosis factor alpha (TNF-α), prostaglandins (PGs), and nitric oxide (NO) in the Stx2induced preterm delivery. EXPERIMENTAL APPROACH.: Pregnant rats were treated with 0.7 ng Stx2/g of body weight and killed at different times after treatment. Placenta and decidua were used to analyze NO synthase (NOS) activity by conversion L-[(14) C]arginine into L-[(14) C]citruline, PGE2 and PGF2α by radioimmunoassay, and cyclooxygenases (COX) protein by Western blot. TNF-α level was analyzed in serum by ELISA and by L929 cytotoxicity. Aminoguanidine (AG, inducible NOS inhibitor), meloxicam (Melo, COX-2 inhibitor) and etanercept (ETA, competitive inhibitor of TNF-α) were used alone or combined to inhibit NO, PGs and TNF-α production respectively, to prevent Stx2-induced preterm delivery. KEY RESULTS.: Stx2 increased placental PGE2 and decidual PGF2α levels as well as COX-2 expression in both tissues. AG and Melo delayed the preterm delivery time but did not prevent it. ETA blocked the TNF-α increase after Stx2 treatment and reduced the preterm delivery by approximately 30%. The combined action of AG and ETA prevented Stx2-induced preterm delivery by roughly 70 %. CONCLUSIONS AND IMPLICATIONS.: Our results demonstrate for the first time that the increase of TNF-α and NO produced by Stx2 are mostly responsible for the preterm delivery in rats. |
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Authors:
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Juliana Burdet; Flavia Sacerdoti; Maximiliano Cella; Ana M Franchi; Cristina Ibarra |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-8 |
Journal Detail:
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Title: British journal of pharmacology Volume: - ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society. |
Affiliation:
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Laboratorio de Fisiopatogenia, Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. |
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