The lipid peroxidation end product 4-hydroxy-2,3-nonenal up-regulates transforming growth factor beta1 expression in the macrophage lineage: a link between oxidative injury and fibrosclerosis.
An increasing number of reports underscore the frequent association of fibrosclerotic diseases of lung, liver, arterial wall, brain, etc., with the accumulation of oxidatively modified lipids and proteins. A cause-and-effect relationship has been proposed between cellular oxidative damage and increased fibrogenesis based on the fact that experimental treatment with antioxidants either prevents or quenches the fibrotic process. With some peculiarities in the different organs, fibrosclerosis is essentially the result of the interaction of macrophages and extracellular matrix-producing cells. The cross-talk is mediated by fibrogenic cytokines, among which the most important appears to be transforming growth factor beta1 (TGF-beta1). This report describes treatment of different types of macrophage, of both human and murine origin, with 4-hydroxy-2,3-nonenal (HNE) a major aldehyde end product of membrane lipid oxidation found consistently to induce both mRNA expression and synthesis of TGF-beta1. Since increased HNE levels have been demostrated in the cirrhotic liver and in the oxidatively modified low-density human lipoproteins associated with atherosclerosis, the up-regulation of macrophage TGF-beta1 by HNE appears to be involved in the pathogenesis of these and similar diseases characterized by fibrosclerosis.
Leonarduzzi
G
G
Department of Experimental Medicine and Oncology, University of Torino, Italy.
Scavazza
A
A
Biasi
F
F
Chiarpotto
E
E
Camandola
S
S
Vogel
S
S
Dargel
R
R
Poli
G
G
D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D015854:Up-Regulation
D000447:Aldehydes; D018808:Transcription Factor AP-1; D016212:Transforming Growth Factor beta; C027576:4-hydroxy-2-nonenal