Role of viral receptors TLR3, RIG-I and MDA5 in mesothelial tissue-type plasminogen activator and plasminogen activator inhibitor-1 synthesis.
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.
Wörnle
Markus
M
Medical Policlinic, Ludwig-Maximillians-University, Munich, Germany. Markus.Woernle@med.uni-muenchen.de
Sauter
Matthias
M
Kastenmüller
Kathrin
K
Ribeiro
Andrea
A
Mussack
Thomas
T
Ladurner
Roland
R
Sitter
Thomas
T
D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology / Q000821:virology; D025461:Feedback, Physiological; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D000072640:Interferon-Induced Helicase, IFIH1; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic; D012704:Serous Membrane / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D034741:RNA, Small Interfering; D012367:RNA, Viral; D011971:Receptors, Immunologic; C051321:SERPINE1 protein, human; D051196:Toll-Like Receptor 3; D005337:Fibrin; D010959:Tissue Plasminogen Activator; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1