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Pulmonary vascular inflammation: effect of TLR signalling on angiopoietin/ TIE regulation
Author(s) -
Hilbert Tobias,
Dornbusch Kathrin,
Baumgarten Georg,
Hoeft Andreas,
Frede Stilla,
Klaschik Sven
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12680
Subject(s) - inflammation , signalling , microbiology and biotechnology , angiopoietin , chemistry , angiopoietin 2 , signalling pathways , signal transduction , immunology , medicine , biology , vegf receptors , vascular endothelial growth factor
Summary Increased pulmonary vascular resistance is a critical complication in sepsis. Toll‐like receptor ( TLR ) as well as angiopoietin ( ANG ) signalling both contribute to the emergence of pulmonary arterial hypertension. We hypothesized that TLR stimulation by bacterial ligands directly affects expression and secretion of ligands and receptors of the angiopoietin/ TIE axis. Microvascular endothelial ( HPMEC ) and smooth muscle cells ( SMC ) of pulmonary origin were incubated with thrombin and with ligands for TLR 2, ‐4, ‐5, and ‐9. Expression and secretion of ANG 1, ‐2, TIE 2 and IL ‐8 were determined using quantitative real‐time PCR and ELISA . TLR stimulation had no impact either on the expression of ANG 2 and TIE 2 in HPMEC or on that of ANG 1 in SMC . However, overall levels of both released ANG 1 and ‐2 were halved upon stimulation with the TLR 9 ligand CpG, and ANG 2 release was significantly enhanced by TLR 4 activation when initially provoked by sequentially performed stimulation. Furthermore, enhanced ANG 2 activity increased endothelial permeability, as demonstrated in an in vitro transwell assay. We conclude that sole TLR stimulation by bacterial ligands plays no significant role for altered expression and secretion of ANG 1, ‐2 and TIE 2 in human pulmonary vascular cells. The interplay between various stimuli is required to induce imbalances between ANG 1 and ‐2.