TY - JOUR
T1 - Modulation of MMP-9 pathway by lycopene in macrophages and fibroblasts exposed to cigarette smoke
AU - Palozza, Paola
AU - Simone, Rossella Emanuela
AU - Catalano, Assunta
AU - Saraceni, Flavia
AU - Celleno, Leonardo
AU - Mele, Maria Cristina
AU - Monego, Giovanni
AU - Cittadini, Achille Renato Maria
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Cigarette smoke extract
KW - Lycopene
KW - MMP-9
KW - Macrophages
KW - Cigarette smoke extract
KW - Lycopene
KW - MMP-9
KW - Macrophages
UR - http://hdl.handle.net/10807/5572
M3 - Article
SN - 1871-5281
SP - 36
EP - 47
JO - Inflammation and Allergy - Drug Targets
JF - Inflammation and Allergy - Drug Targets
ER -