It is now well accepted that oxysterols play important roles in the formation of atherosclerotic plaque, involving cytotoxic, pro-oxidant and pro-inflammatory processes. It has been recently suggested that tomato lycopene may act as a preventive agent in atherosclerosis, although the exact mechanism of such a protection is not clarified. The main aim of this study was to investigate whether lycopene is able to counteract oxysterol-induced pro-inflammatory cytokines cascade in human macrophages, limiting the formation of atherosclerotic plaque. Therefore, THP-1 macrophages were exposed to two different oxysterols, such as 7-keto-cholesterol (7-KC) (4-16 μM) and 25- hydroxycholesterol (25-OHC) (2-4 μM), alone and in combination with lycopene (0.5-2 μM). Both oxysterols enhanced pro-inflammatory cytokine (IL-1β, IL-6, IL-8, TNFα) secretion and mRNA levels in a dose-dependent manner, although at different extent. These effects were associated with an increased reactive oxygen species (ROS) production through an enhanced expression of NAD(P)H oxidase (NOX-4). Moreover, a net increment of phosphorylation of ERK1/2, p-38 and JNK and of nuclear factor kB (NF-kB) nuclear binding was observed. Lycopene prevented oxysterol-induced increase in pro-inflammatory citokine secretion and expression. Such an effect was accompanied by an inhibition of oxysterol-induced ROS production, MAPK phosphorylation and NF-kB activation. Moreover, the carotenoid increased PPARγ levels in THP-1 macrophages. Taken all together, these data bring new information on the anti-atherogenic properties of lycopene, and on its mechanisms of action in atherosclerosis prevention.

Palozza, P., Simone, R. E., Catalano, A., Monego, G., Barini, A., Mele, M. C., Ranelletti, F. O., Lycopene prevention of oxysterol-induced pro-inflammatory cytokine cascade in human macrophages: inhibition of NF-kB nuclear binding and increase in PPARgamma; expression, <<JOURNAL OF NUTRITIONAL BIOCHEMISTRY>>, 2011; (22): 259-268 [http://hdl.handle.net/10807/5281]

Lycopene prevention of oxysterol-induced pro-inflammatory cytokine cascade in human macrophages: inhibition of NF-kB nuclear binding and increase in PPARgamma; expression

Palozza, Paola;Simone, Rossella Emanuela;Catalano, Assunta;Monego, Giovanni;Barini, Angelina;Mele, Maria Cristina;Ranelletti, Franco Oreste
2010

Abstract

It is now well accepted that oxysterols play important roles in the formation of atherosclerotic plaque, involving cytotoxic, pro-oxidant and pro-inflammatory processes. It has been recently suggested that tomato lycopene may act as a preventive agent in atherosclerosis, although the exact mechanism of such a protection is not clarified. The main aim of this study was to investigate whether lycopene is able to counteract oxysterol-induced pro-inflammatory cytokines cascade in human macrophages, limiting the formation of atherosclerotic plaque. Therefore, THP-1 macrophages were exposed to two different oxysterols, such as 7-keto-cholesterol (7-KC) (4-16 μM) and 25- hydroxycholesterol (25-OHC) (2-4 μM), alone and in combination with lycopene (0.5-2 μM). Both oxysterols enhanced pro-inflammatory cytokine (IL-1β, IL-6, IL-8, TNFα) secretion and mRNA levels in a dose-dependent manner, although at different extent. These effects were associated with an increased reactive oxygen species (ROS) production through an enhanced expression of NAD(P)H oxidase (NOX-4). Moreover, a net increment of phosphorylation of ERK1/2, p-38 and JNK and of nuclear factor kB (NF-kB) nuclear binding was observed. Lycopene prevented oxysterol-induced increase in pro-inflammatory citokine secretion and expression. Such an effect was accompanied by an inhibition of oxysterol-induced ROS production, MAPK phosphorylation and NF-kB activation. Moreover, the carotenoid increased PPARγ levels in THP-1 macrophages. Taken all together, these data bring new information on the anti-atherogenic properties of lycopene, and on its mechanisms of action in atherosclerosis prevention.
Inglese
Palozza, P., Simone, R. E., Catalano, A., Monego, G., Barini, A., Mele, M. C., Ranelletti, F. O., Lycopene prevention of oxysterol-induced pro-inflammatory cytokine cascade in human macrophages: inhibition of NF-kB nuclear binding and increase in PPARgamma; expression, <<JOURNAL OF NUTRITIONAL BIOCHEMISTRY>>, 2011; (22): 259-268 [http://hdl.handle.net/10807/5281]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/5281
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