Hepatitis C Virus Induced Endothelial Inflammatory Response Depends on the Functional Expression of TNF alpha Receptor Subtype 2

作者：Pircher Joachim; Czermak Thomas; Merkle Monika; Mannell Hanna; Kroetz Florian; Ribeiro Andrea; Vielhauer Volker; Nadjiri Jonathan; Gaitzsch Erik; Niemeyer Markus; Porubsky Stefan; Groene Hermann Josef; Woernle Markus

来源：PLos One, 2014, 9(11): e113351.

DOI：10.1371/journal.pone.0113351

In hepatitis C virus (HCV) infection, morbidity and mortality often result from extrahepatic disease manifestations. We provide evidence for a role of receptors of the innate immune system in virally induced inflammation of the endothelium in vitro and in vivo. Corresponding to the in vitro finding of an HCV-dependent induction of proinflammatory mediators in endothelial cells, mice treated with poly (I: C) exhibit a significant reduction in leukocyte rolling velocity, an increase in leukocyte adhesion to the vessel wall and an increased extravasation of leukocytes. HCV directly promotes activation, adhesion and infiltration of inflammatory cells into the vessel wall by activation of endothelial viral receptors. Poly (I: C) induces the expression of TLR3 in vivo and hereby allows for amplification of all of the aforementioned responses upon viral infection. Proinflammatory effects of viral RNA are specifically mediated by TLR3 and significantly enhanced by tumor necrosis factor alpha (TNFa). HCV-RNA induces the endothelial expression of TNFa and TNFa receptor subtype 2 and we provide evidence that leucocyte adhesion and transmigration in response to activation of viral RNA receptors seem to depend on expression of functional TNFR2. Our results demonstrate that endothelial cells actively participate in immune mediated vascular inflammation caused by viral infections.

• 出版日期2014-11-24