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

Maria Cristina Mele, Giovanni Monego, Paola Palozza, Assunta Catalano, Leonardo Celleno, Achille Renato Maria Cittadini, Rossella Emanuela Simone, Flavia Saraceni

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

11 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)36-47
Numero di pagine12
RivistaINFLAMMATION & ALLERGY - DRUG TARGETS
Stato di pubblicazionePubblicato - 2012

Keywords

  • Cigarette smoke extract
  • Lycopene
  • MMP-9
  • Macrophages

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