α-Melanocyte-stimulating hormone inhibits lung injury after renal ischemia/reperfusion

• Published in: American journal of respiratory and critical care medicine 2004-03, Vol.169 (6), p.749-756
• Main Authors: JIANGPING DENG, XUZHEN HU, YUEN, Peter S. T, STAR, Robert A
• Format: Article
• Language: English
• Subjects: alpha-MSH - physiology; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Gene Expression Regulation - physiology; Intensive care medicine; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Kidney - blood supply; Lung - metabolism; Lung - pathology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - physiopathology; RNA, Messenger - genetics; Stress, Physiological - metabolism; Stress, Physiological - physiopathology; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200303-372oc

Combined acute renal and pulmonary failure has a very high mortality. In animals, lung injury develops after shock or visceral or renal ischemia. Alpha-melanocyte-stimulating hormone (alpha-MSH) is an antiinflammatory cytokine, which inhibits inflammatory, apoptotic, and cytotoxic pathways implicated in acute renal injury. We sought to determine if alpha-MSH inhibits acute lung injury after renal ischemia and to determine the early mechanisms of alpha-MSH action. Mice were subjected to renal ischemia treated with vehicle or alpha-MSH. At early time points, we measured organ histology, leukocyte accumulation, myeloperoxidase activity, activation of nuclear factor-kappaB, p38 mitogen-activated protein kinase, c-Jun, and activator protein-1 pathways, in addition to messenger RNA for intracellular adhesion molecule-1 and tumor necrosis factor-alpha. Renal ischemia rapidly activated kidney and lung nuclear factor-kappaB, p38 mitogen-activated protein kinase, c-Jun, and activator protein-1 pathways, and distant lung injury. Alpha-MSH administration immediately before reperfusion significantly decreased kidney and lung injury and prevented activation of kidney and lung transcription factors and stress response genes, and lung intracellular adhesion molecule-1 and tumor necrosis factor-alpha at early time points after renal ischemia/reperfusion. We conclude that distant lung injury occurs rapidly after renal ischemia. alpha-MSH protects against both kidney and lung damage after renal ischemia, in part, by inhibiting activation of transcription factors and stress genes early after renal injury.