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Published on: January 10, 2015
Lycopene inhibits NF-kB-mediated IL-8 expression and changes redox and PPARγ signalling in cigarette smoke-stimulated
Rossella E Simone1, Marco Russo, Assunta Catalano
1Institute of General Pathology, Catholic University, Rome, Italy.
Abstract:
Increasing evidence suggests that lycopene, the major carotenoid present in tomato, may be preventive against smoke-induced cell damage. However, the mechanisms of such a prevention are still unclear. The aim of this study was to investigate the role of lycopene on the production of the pro-inflammatory cytokine IL-8 induced by cigarette smoke and the possible mechanisms implicated. Therefore, human THP-1 macrophages were exposed to cigarette smoke extract (CSE), alone and following a 6-h pre-treatment with lycopene (0.5-2 µM). CSE enhanced IL-8 production in a time- and a dose-dependent manner. Lycopene pre-treatment resulted in a significant inhibition of CSE-induced IL-8 expression at both mRNA and protein levels. NF-kB controlled the transcription of IL-8 induced by CSE, since PDTC prevented such a production. Lycopene suppressed CSE-induced NF-kB DNA binding, NF-kB/p65 nuclear translocation and phosphorylation of IKKα and IkBα. Such an inhibition was accompanied by a decrease in CSE-induced ROS production and NOX-4 expression. Lycopene further inhibited CSE-induced phosphorylation of the redox-sensitive ERK1/2, JNK and p38 MAPKs. Moreover, the carotenoid increased PPARγ levels which, in turn, enhanced PTEN expression and decreased pAKT levels in CSE-exposed cells. Such effects were abolished by the PPARγ inhibitor GW9662. Taken together, our data indicate that lycopene prevented CSE-induced IL-8 production through a mechanism involving an inactivation of NF-kB. NF-kB inactivation was accompanied by an inhibition of redox signalling and an activation of PPARγ signalling. The ability of lycopene in inhibiting IL-8 production, NF-kB/p65 nuclear translocation, and redox signalling and in increasing PPARγ expression was also found in isolated rat alveolar macrophages exposed to CSE. These findings provide novel data on new molecular mechanisms by which lycopene regulates cigarette smoke-driven inflammation in human macrophages.
Insights
Lycopene, found in tomatoes, prevents cigarette smoke-induced inflammation by inhibiting the NF-kB pathway and reducing oxidative stress. This study reveals lycopene
Area of Science:
- Immunology
- Molecular Biology
- Nutritional Science
Background:
- Cigarette smoke exposure triggers inflammatory responses in macrophages, contributing to various diseases.
- Interleukin-8 (IL-8) is a key pro-inflammatory cytokine implicated in smoke-induced lung damage.
- The precise molecular mechanisms by which dietary compounds like lycopene modulate smoke-induced inflammation are not fully understood.
Purpose of the Study:
- To investigate the inhibitory effect of lycopene on cigarette smoke extract (CSE)-induced IL-8 production in human macrophages.
- To elucidate the underlying molecular mechanisms, including the roles of NF-kB, redox signaling, and PPARγ.
Main Methods:
- Human THP-1 macrophages and rat alveolar macrophages were exposed to CSE with or without lycopene pre-treatment.
- Assessed IL-8 mRNA and protein levels, NF-kB activation (DNA binding, nuclear translocation), IKKα/IkBα phosphorylation, ROS production, NOX-4 expression, MAPK phosphorylation, and PPARγ/PTEN/pAKT signaling.
- Utilized PDTC and GW9662 as pathway inhibitors.
Main Results:
- Lycopene significantly inhibited CSE-induced IL-8 production at both mRNA and protein levels.
- Lycopene suppressed CSE-induced NF-kB activation, ROS generation, NOX-4 expression, and phosphorylation of ERK1/2, JNK, and p38 MAPKs.
- Lycopene increased PPARγ levels, leading to enhanced PTEN and decreased pAKT, effects reversed by GW9662.
Conclusions:
- Lycopene effectively prevents cigarette smoke-induced IL-8 production in macrophages via NF-kB inactivation.
- This protective effect involves the inhibition of redox signaling pathways and the activation of PPARγ signaling.
- Findings highlight lycopene's potential as a dietary intervention against smoke-induced inflammation through novel molecular mechanisms.
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