دورية أكاديمية
A complex interaction between Rickettsia conorii and Dickkopf-1--potential role in immune evasion mechanisms in endothelial cells.
العنوان: | A complex interaction between Rickettsia conorii and Dickkopf-1--potential role in immune evasion mechanisms in endothelial cells. |
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المؤلفون: | Elisabeth Astrup, Tove Lekva, Giovanni Davì, Kari Otterdal, Francesca Santilli, Erik Oie, Bente Halvorsen, Jan Kristian Damås, Didier Raoult, Giustina Vitale, Juan P Olano, Thor Ueland, Pål Aukrust |
المصدر: | PLoS ONE, Vol 7, Iss 9, p e43638 (2012) |
بيانات النشر: | Public Library of Science (PLoS), 2012. |
سنة النشر: | 2012 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | The pathophysiological hallmark of spotted fever group rickettsioses comprises vascular inflammation. Based on the emerging importance of the wingless (Wnt) pathways in inflammation and vascular biology, we hypothesized that Dickkopf-1 (DKK-1), as a major modulator of Wnt signaling, could be involved in the pathogenesis in rickettsial infections. Our major findings were: (i) While baseline concentration of DKK-1 in patients with R. conorii infection (n = 32) were not different from levels in controls (n = 24), DKK-1 rose significantly from presentation to first follow-up sample (median 7 days after baseline). (ii) In vitro experiments in human umbilical vein endothelial cells (HUVECs) showed that while heat-inactivated R. conorii enhanced the release of interleukin-6 (IL-6) and IL-8, it down-regulated the release of endothelial-derived DKK-1 in a time- and dose-dependent manner. (iii) Silencing of DKK-1 attenuated the release of IL-6, IL-8 and growth-related oncogene (GRO)α in R. conorii-exposed HUVECs, suggesting inflammatory effects of DKK-1. (iv) Silencing of DKK-1 attenuated the expression of tissue factor and enhanced the expression of thrombomodulin in R. conorii-exposed HUVECs suggesting pro-thrombotic effects of DKK-1. The capacity of R. conorii to down-regulate endothelial-derived DKK-1 and the ability of silencing DKK-1 to attenuate R. conorii-induced inflammation in endothelial cells could potentially reflect a novel mechanism by which R. conorii escapes the immune response at the site of infection. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1932-6203 80986668 |
العلاقة: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028464/?tool=EBITest; https://doaj.org/toc/1932-6203Test |
DOI: | 10.1371/journal.pone.0043638 |
الوصول الحر: | https://doaj.org/article/9484bb1dd85a464d80986668876ab5deTest |
رقم الانضمام: | edsdoj.9484bb1dd85a464d80986668876ab5de |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19326203 80986668 |
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DOI: | 10.1371/journal.pone.0043638 |