RESUMEN
Growth hormone-releasing hormone antagonists (GHRHAnt) have been associated with antitumor and antioxidative activities. The present study investigates for the first time the effects of those compounds towards pro-inflammatory cytokine expression in a murine model of cecal ligation and puncture (CLP) - induced sepsis. The results indicate that GHRHAnt JV-1-36 significantly suppressed IL-1α, IL-6, and pSTAT3 activation in septic lungs. Moreover, GHRHAnt treatment reduced bronchoalveolar lavage fluid (BALF) protein concentration, suggesting a protective effect of that compound in sepsis-induced lung edema. Based on those findings, it is suggested that GHRHAnt may represent an exciting new therapeutic possibility in sepsis-induced endotoxemia and lung injury.
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento , Pulmón , Sepsis , Animales , Sepsis/tratamiento farmacológico , Hormona Liberadora de Hormona del Crecimiento/antagonistas & inhibidores , Hormona Liberadora de Hormona del Crecimiento/metabolismo , Ratones , Pulmón/patología , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Masculino , Factor de Transcripción STAT3/metabolismo , Líquido del Lavado Bronquioalveolar , Interleucina-6/metabolismo , Modelos Animales de EnfermedadRESUMEN
The endothelium constitutes the innermost lining of the blood vessels and controls blood fluidity, vessel permeability, platelet aggregation, and vascular tone. Endothelial dysfunction plays a key role in initiating a vascular inflammatory cascade and is the pivotal cause of various devastating diseases in multiple organs including the heart, lung, kidney, and brain. Glucocorticoids have traditionally been used to combat vascular inflammation. Endothelial cells express glucocorticoid receptors (GRs), and recent studies have demonstrated that endothelial GR negatively regulates vascular inflammation in different pathological conditions such as sepsis, diabetes, and atherosclerosis. Mechanistically, the anti-inflammatory effects of GR are mediated, in part, through the suppression of Wnt signaling. Moreover, GR modulates the fatty acid oxidation (FAO) pathway in endothelial cells and hence can influence FAO-mediated fibrosis in several organs including the kidneys. This review summarizes the relationship between GR and Wnt signaling in endothelial cells and the effects of the Wnt pathway in different cardiac and renal diseases. Available data suggest that GR plays a significant role in restoring endothelial integrity, and research on endothelial GR-Wnt interactions could facilitate the development of novel therapies for many cardiorenal conditions.
