Document Detail

Viral Toll Like Receptor activation of pulmonary vascular smooth muscle cells results in endothelin-1 generation; relevance to pathogenesis of pulmonary arterial hypertension.
MedLine Citation:
PMID:  22960172     Owner:  NLM     Status:  MEDLINE    
Pulmonary arterial hypertension (PAH) is a rare but fatal condition in which raised pulmonary vascular resistance leads to right heart failure and death. Endothelin-1 is a potent endogenous vasoconstrictor, which is considered to be central to many of the events that lead to PAH, and is an important therapeutic target in the treatment of the condition. In many cases of PAH, the aetiology is unknown but inflammation is increasingly thought to play an important role and viruses have been implicated in the development of disease. The Toll Like Receptors (TLRs) play a key role in innate immune responses by initiating specific anti-bacterial and anti-viral defences in recognition of signature molecular motifs on the surface of invading pathogens. In this study, we set out to examine the expression of bacterial and viral TLRs in human pulmonary artery smooth muscle cells and to establish whether their activation could be relevant to PAH. We found that the viral TLR3 and bacterial TLRs 4 and 6 were most abundantly expressed in human pulmonary artery smooth muscle cells. Using specific TLR ligands, we found that activation of TLRs 3 and 4 resulted in IL-8 release by human pulmonary artery smooth muscle cells but that only TLR3 stimulation resulted in IP10 and endothelin-1 release. These data suggest that human pulmonary artery smooth muscle cells express significant levels of viral TLR3 and respond to its activation by releasing endothelin-1. This may have importance in understanding the association between viruses and the development of PAH.
Peter M George; Rekha Badiger; Dongmin Shao; Michael R Edwards; Stephen J Wort; Mark J Paul-Clark; Jane A Mitchell
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-28
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  426     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-09     Completed Date:  2013-02-12     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  486-91     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Cells, Cultured
Chemokines / genetics
Cytokines / genetics
Endothelin-1 / biosynthesis*
Gene Expression
Hypertension, Pulmonary / metabolism*,  virology
Interleukin-8 / genetics
Muscle, Smooth, Vascular / metabolism*,  virology
Myocytes, Smooth Muscle / metabolism*,  virology
Poly I-C / pharmacology
Receptors, Cytokine / genetics
Toll-Like Receptor 3 / agonists,  genetics,  metabolism*
Tumor Necrosis Factor-alpha / pharmacology
Grant Support
G1100400//Medical Research Council; //Medical Research Council
Reg. No./Substance:
0/Chemokines; 0/Cytokines; 0/Endothelin-1; 0/IP10-Mig receptor; 0/Interleukin-8; 0/Receptors, Cytokine; 0/TLR3 protein, human; 0/Toll-Like Receptor 3; 0/Tumor Necrosis Factor-alpha; 24939-03-5/Poly I-C

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