Alpha-melanocyte-stimulating hormone inhibits lung injury after renal ischemia/reperfusion.
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.
Deng
Jiangping
J
Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1268, USA.
Hu
Xuzhen
X
Yuen
Peter S T
PS
Star
Robert A
RA
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000098:blood supply*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000521:alpha-MSH / Q000502:physiology*
D012333:RNA, Messenger; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000521:alpha-MSH