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ABSTRACT: Dietary intakes of tomatoes and tomato products containing lycopene have been shown to be associated with decreased risk of chronic diseases, such as cancer. Although several mechanisms, including modulation of gap junction communication and enhancement of immune system, are thought to be implicated in its beneficial activities, evidence is accumulating to suggest that lycopene may act as a modulator of intracellular reactive oxygen species (ROS) and, therefore, control ROS-mediated cell growth. According with this, at high concentration, ROS have been reported to be hazardous for living organisms, whereas at moderate concentrations, they play an important role as regulatory mediators in signaling processes regulating cell growth. In this review, we report the available evidence on a role of lycopene as a redox agent in cell proliferation, differentiation and apoptosis. In particular, we focused our attention on lycopene prevention of cell oxidative damage and its influence in cell growth as well as on lycopene modulation of redox-sensitive molecular targets in cell signalling: growth factors and growth factor receptors, antioxidant response elements, MAPKs, transcription factors, such as NF-kB and AP-1, and cytokine expression. Moreover, we speculate on the possible influence that lycopene may have as a redox agent in cancer.
Current Medicinal Chemistry 04/2011; 18(12):1846-60. · 4.86 Impact Factor
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ABSTRACT: Lycopene, a natural carotenoid found in tomato, has been reported to possess various health benefits, such as cardiovascular and cancer preventive properties. However, the experimental basis for such health benefits is not fully understood. One of the possible mechanisms for its protective activities is by down-regulation of the inflammatory response. That includes the inhibition of pivotal pro-inflammatory mediators, such as the reduction of reactive oxygen species, the inhibition of synthesis and release of pro-inflammatory cytokines, changes in the expression of cyclooxygenase and lipoxygenase, modifications of eicosanoid synthesis, and modulation of signal transduction pathways, including that of the inducible nitric oxide synthase via its inhibitory effects on Nuclear Factor-kB (NF-kB), Activated protein-1 (AP-1) and mitogen-activated protein kinase (MAPK) signaling. Recent data suggest that lycopene also exhibits anti-inflammatory activity through induction of programmed cell death in activated immune cells. This review will discuss recent data on the control of inflammatory signaling exerted by tomato lycopene in isolated cells, in animal models and in clinical trials, focusing on the dose of the carotenoid and the biological environment in which it acts. A clear understanding of the molecular mechanisms of action of lycopene is crucial in the valuation of this molecule as a potential preventive and therapeutic agent.
Current Medicinal Chemistry 01/2010; 17(23):2547-63. · 4.86 Impact Factor
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C. Lunardi,
C. Bason,
M. Dolcino,
R. Navone, R. Simone,
D. Saverino,
L. Frulloni,
E. Tinazzi,
D. Peterlana,
R. Corrocher,
A. Puccetti
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ABSTRACT: Background and objectives. Bacterial flagellin is considered an important antigen in Crohn’s disease (CD) as it activates innate immunity through Toll-Like Receptor 5 (TLR5) engagement and induces an elevated adaptive immune response. Little is known about the presence of an autoimmune process in CD. We aimed to identify pathogenically relevant autoantigen targets in CD.Methods. We screened a random peptide library with pooled sera of patients with active CD. Transepithelial flux of [3H] mannitol in T84 human intestinal epithelial cell line was used to study the epithelial barrier function. Monocyte activation was evaluated by surface expression of activation markers and by production of pro-inflammatory cytokines. Gene modulation of T84 cells exposed to antipeptide antibodies was analysed by gene array.Results. We identified a peptide that shares homology with Salmonella typhimurium flagellin and with self-antigens such as TLR5 and cell junction protein, Pals 1-associated tight junction protein. The affinity-purified antipeptide antibodies recognized the self-antigens and induced increased intestinal epithelial cell permeability. Moreover, the antibodies induced monocyte activation upon binding TLR5. Finally, in cultured intestinal cells (T84) the purified antibodies induced the modulation of clusters of proinflammatory genes similar to the one induced by the engagment of TLR5 by its natural ligand flagellin.Conclusions. Antibodies directed against an immunodominant peptide of flagellin recognize self-antigens and are functionally active suggesting the presence of an autoimmune process that can both facilitate loss of tolerance to intestinal microflora by increasing cell permeability and amplify the innate immunity involvement through a novel mechanism of TLR5 activation.
Journal of Internal Medicine 01/2009; 265(2):250 - 265. · 5.48 Impact Factor
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C Lunardi,
C Bason,
M Dolcino,
R Navone, R Simone,
D Saverino,
L Frulloni,
E Tinazzi,
D Peterlana,
R Corrocher,
A Puccetti
[show abstract]
[hide abstract]
ABSTRACT: Bacterial flagellin is considered an important antigen in Crohn's disease (CD) as it activates innate immunity through Toll-Like Receptor 5 (TLR5) engagement and induces an elevated adaptive immune response. Little is known about the presence of an autoimmune process in CD. We aimed to identify pathogenically relevant autoantigen targets in CD.
We screened a random peptide library with pooled sera of patients with active CD. Transepithelial flux of [3H] mannitol in T84 human intestinal epithelial cell line was used to study the epithelial barrier function. Monocyte activation was evaluated by surface expression of activation markers and by production of pro-inflammatory cytokines. Gene modulation of T84 cells exposed to antipeptide antibodies was analysed by gene array.
We identified a peptide that shares homology with Salmonella typhimurium flagellin and with self-antigens such as TLR5 and cell junction protein, Pals 1-associated tight junction protein. The affinity-purified antipeptide antibodies recognized the self-antigens and induced increased intestinal epithelial cell permeability. Moreover, the antibodies induced monocyte activation upon binding TLR5. Finally, in cultured intestinal cells (T84) the purified antibodies induced the modulation of clusters of proinflammatory genes similar to the one induced by the engagement of TLR5 by its natural ligand flagellin.
Antibodies directed against an immunodominant peptide of flagellin recognize self-antigens and are functionally active suggesting the presence of an autoimmune process that can both facilitate loss of tolerance to intestinal microflora by increasing cell permeability and amplify the innate immunity involvement through a novel mechanism of TLR5 activation.
Journal of Internal Medicine 10/2008; 265(2):250-65. · 5.48 Impact Factor
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Allergologia et Immunopathologia 38(6):341-3. · 1.04 Impact Factor
