Matrix metalloproteinase-9 (MMP-9) has been implicated in both inflammation and fibrosis. It has been reported that cigarette smoke induced MMP-9 expression and that lycopene may act as an anti-inflammatory agent and may counteract several signal pathways affected by cigarette smoke exposure. However, at the moment, it is unknown if lycopene may inhibit cigarette smoke-induced MMP-9 expression. Presently, we examined the inhibitory mechanism of lycopene on MMP-9 induction in cultured human macrophages (THP-1 cells), in isolated rat alveolar macrophages (AMs) and in cultured RAT-1 fibroblasts, all cellular sources of MMP-9, exposed to cigarette smoke extract (CSE). CSE induced a marked increase in MMP-9 expression in cultured as well as in isolated cells. A 8 h-lycopene pre-treatment (0.5-2 μM) reduced CSE-mediated MMP-9 induction in a dose- and time-dependent manner. Lycopene attenuated CSE-mediated activation of Ras, enhancing the levels of this protein in the cytosolic fraction. Moreover, lycopene inhibited CSE-induced ERK1/2 and NF-kB activation in a dose-dependent manner. Lycopene-mediated inhibition of MMP-9 was reversed by mevalonate and associated with a reduced expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Taken together, these results suggest that lycopene may inhibit CSE-mediated MMP-9 induction, primarily by blocking prenylation of Ras in a signaling pathway, in which MEK1/2-ERK1/2 and NF-kB are involved.

Palozza, P., Simone, R. E., Catalano, A., Saraceni, F., Celleno, L., Mele, M. C., Monego, G., Cittadini, A., Modulation of MMP-9 pathway by lycopene in macrophages and fibroblasts exposed to cigarette smoke, <<INFLAMMATION & ALLERGY - DRUG TARGETS>>, 2012; (11): 36-47 [http://hdl.handle.net/10807/5572]

Modulation of MMP-9 pathway by lycopene in macrophages and fibroblasts exposed to cigarette smoke

Palozza, Paola;Catalano, Assunta;Celleno, Leonardo;Mele, Maria Cristina;Monego, Giovanni;Cittadini, Achille
2012

Abstract

Matrix metalloproteinase-9 (MMP-9) has been implicated in both inflammation and fibrosis. It has been reported that cigarette smoke induced MMP-9 expression and that lycopene may act as an anti-inflammatory agent and may counteract several signal pathways affected by cigarette smoke exposure. However, at the moment, it is unknown if lycopene may inhibit cigarette smoke-induced MMP-9 expression. Presently, we examined the inhibitory mechanism of lycopene on MMP-9 induction in cultured human macrophages (THP-1 cells), in isolated rat alveolar macrophages (AMs) and in cultured RAT-1 fibroblasts, all cellular sources of MMP-9, exposed to cigarette smoke extract (CSE). CSE induced a marked increase in MMP-9 expression in cultured as well as in isolated cells. A 8 h-lycopene pre-treatment (0.5-2 μM) reduced CSE-mediated MMP-9 induction in a dose- and time-dependent manner. Lycopene attenuated CSE-mediated activation of Ras, enhancing the levels of this protein in the cytosolic fraction. Moreover, lycopene inhibited CSE-induced ERK1/2 and NF-kB activation in a dose-dependent manner. Lycopene-mediated inhibition of MMP-9 was reversed by mevalonate and associated with a reduced expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Taken together, these results suggest that lycopene may inhibit CSE-mediated MMP-9 induction, primarily by blocking prenylation of Ras in a signaling pathway, in which MEK1/2-ERK1/2 and NF-kB are involved.
Inglese
Palozza, P., Simone, R. E., Catalano, A., Saraceni, F., Celleno, L., Mele, M. C., Monego, G., Cittadini, A., Modulation of MMP-9 pathway by lycopene in macrophages and fibroblasts exposed to cigarette smoke, <>, 2012; (11): 36-47 [http://hdl.handle.net/10807/5572]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/5572
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