Extracorporeal shock waves: from lithotripsy to anti-inflammatory action by NO production.
At low energy density (0.03 mJ/mm2), extracorporeal shock waves (ESW), originally developed for clinical lithotripsy, have successfully been used for anti-inflammatory treatment of soft tissues. Since nitric oxide plays a critical role in inflammation, we hypothesized for ESW to increase NO production in cells. Using human umbilical vein endothelial cells as a model system, we observed that ESW, at low energy density, rapidly induced an enhancement of eNOS activity. In these cells, eNOS activity is modulated by tyrosine- and serine-phosphorylation. ESW shifted eNOS to a less-tyrosine-phosphorylated form, without affecting its serine-phosphorylation, thus accounting for its rapid enzyme activation. LPS/IFN-gamma treatment of human umbilical vein endothelial cells induced a rapid inhibition of eNOS activity and concomitant NF-kappaB activation which were efficiently counteracted by ESW treatment. Therefore, the present results indicate that the molecular mechanism of clinically observed anti-inflammatory action of ESW should include tyrosine-dephosphorylation of eNOS, a successive increase in NO production and suppression of NF-kappaB activation.
Mariotto
Sofia
S
Department of Neuroscience and Vision, Section of Biochemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
Cavalieri
Elisabetta
E
Amelio
Ernesto
E
Ciampa
Anna Rosa
AR
de Prati
Alessandra Carcereri
AC
Marlinghaus
Ernst
E
Russo
Sergio
S
Suzuki
Hisanori
H
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008096:Lithotripsy; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D012694:Serine / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D014443:Tyrosine; D012694:Serine; D007371:Interferon-gamma; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III