Shockwave therapy differentially stimulates endothelial cells: implications on the control of inflammation via toll-Like receptor 3.
Shock wave therapy (SWT) reportedly improves ventricular function in ischemic heart failure. Angiogenesis and inflammation modulatory effects were described. However, the mechanism remains largely unknown. We hypothesized that SWT modulates inflammation via toll-like receptor 3 (TLR3) through the release of cytosolic RNA. SWT was applied to human umbilical vein endothelial cells (HUVECs) with 250 impulses, 0.08 mJ/mm(2) and 3 Hz. Gene expression of TLR3, inflammatory genes and signalling molecules was analysed at different time points by real-time polymerase chain reaction. SWT showed activation of HUVECs: enhanced expression of TLR3 and of the transporter protein for nucleic acids cyclophilin B, of pro-inflammatory cytokines cyclophilin A and interleukin-6 and of anti-inflammatory interleukin-10. No changes were found in the expression of vascular endothelial cell adhesion molecule. SWT modulates inflammation via the TLR3 pathway. The interaction between interleukin (IL)-6 and IL-10 in TLR3 stimulation can be schematically seen as a three-phase regulation over time.
Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
Johannes
J
Holfeld
Can
C
Tepeköylü
Radoslaw
R
Kozaryn
Anja
A
Urbschat
Kai
K
Zacharowski
Michael
M
Grimm
Patrick
P
Paulus
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured; D021984:Cyclophilin A / Q000096:biosynthesis / Q000276:immunology; D021983:Cyclophilins / Q000096:biosynthesis / Q000276:immunology; D006333:Heart Failure / Q000628:therapy*; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000628:therapy*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D018919:Neovascularization, Physiologic / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D012038:Regeneration; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D019010:Vascular Cell Adhesion Molecule-1; D016753:Interleukin-10; C081786:cyclophilin B; D021984:Cyclophilin A; D021983:Cyclophilins; D011070:Poly I-C