Toll-like Receptor 3 Is a Therapeutic Target for Pulmonary Hypertension

• DOI: 10.1164/rccm.201707-1370oc
• Publication Date: 2018-09-13T14:43:49Z
• Authors: Daniela Farkas; A. A. Roger Thompson; Aneel R. Bhagwani; Schuyler Hultman; Hyun Ji; Naveen Kotha; Grant Farr; Nadine D. Arnold; Adam Braithwaite; Helen Casbolt; Jennifer E. Cole; Ian Sabroe; Claudia Monaco; Carlyne D. Cool; Elena A. Goncharova; Allan Lawrie; Laszlo Farkas
• Keywords: TLR3; Hypoxia

Pulmonary arterial hypertension (PAH) is characterized by vascular cell proliferation and endothelial apoptosis. TLR3 (Toll-like receptor 3) a for double-stranded RNA has been recently implicated in protection.To study the expression role of PAH to determine whether agonist reduces pulmonary preclinical models.Lung tissue cells from patients with were investigated polymerase chain reaction, immunofluorescence, apoptosis assays. TLR3-/- TLR3+/+ mice exposed chronic hypoxia SU5416. Chronic or hypoxia/SU5416 rats treated polyinosinic/polycytidylic acid (Poly[I:C]).TLR3 was reduced patient lung cells, exhibited more severe following exposure hypoxia/SU5416. knockdown promoted signaling via other intracellular receptors cells. This associated greater susceptibility apoptosis, known driver remodeling. Poly(I:C) increased IL-10 rat In vivo, high-dose both models proof-of-principle experiments. addition, also right ventricular failure established hypertension.Our work identifies novel based on findings that contributes