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.

Plos One
|June 1, 2011
PubMed

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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