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Thromb Haemost 2009; 101(06): 1128-1137
DOI: 10.1160/TH08-11-0744
Wound Healing and Inflammation/Infection
Schattauer GmbH

Role of viral receptors TLR3, RIG-I and MDA5 in mesothelial tissue-type plasminogen activator and plasminogen activator inhibitor-1 synthesis

Markus Wörnle
1   Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
,
Matthias Sauter
1   Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
,
Kathrin Kastenmüller
1   Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
,
Andrea Ribeiro
1   Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
,
Thomas Mussack
2   Department of Surgery, Ludwig-Maximilians-University, Munich, Germany
,
Roland Ladurner
2   Department of Surgery, Ludwig-Maximilians-University, Munich, Germany
,
Thomas Sitter
1   Medical Policlinic, Ludwig-Maximilians-University, Munich, Germany
› Author AffiliationsFinancial support: This work was supported from the Else-Kröner-Fresenius-Stiftung by a grant to Matthias Sauter and Thomas Sitter and from the Deutsche Nierenstiftung by a grant to Markus Wörnle.
Further Information

Publication History

Received: 17 November 2008

Accepted after major revision: 18 March 2009

Publication Date:
24 November 2017 (online)

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Summary

Tissue-type plasminogen activator (t-PA) and its specific inhibitor plasminogen activator inhibitor-1 (PAI-1) are key mediators in the regulation of fibrin generation and fibrinolysis. Mesothelial cells (MC) line the inner surface of serosal cavities and are a source of procoagulant and fibrinolytic system components. Viral inflammation and infection of MC are a major problem in several organ systems including pleura, pericardium and peritoneum. MC express the viral receptors Toll-like receptor 3 (TLR3), RIG-I and MDA5. TLRs recognise molecular patterns associated with microbial pathogens and induce an immune response. TLR3 recognises dsRNA of viral origin as exemplified by poly (I:C) RNA, a synthetic analogue of viral dsRNA. The helicases RIG-I and MDA5 may also act as sensors of viral infections. Activation of these receptors by poly (I:C) RNA leads to an time- and dose-dependent increase of mesothelial PAI-1 synthesis and a decrease of t-PA expression. To show the specific effect of viral receptors knockdown experiments with siRNA specific for TLR3, RIG-I and MDA5 were performed. This finding of viral induced changes of t-PA and PAI-1 synthesis may indicate a novel link between viral infections and formation of mesothelial fibrin deposits and progression of viral associated disease of the pleura, peritoneum and pericardium.

Keywords

Mesothelial - MDA5 - PAI-1 - RIG-I - Toll-like receptor 3
 

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