Lycopene prevention of oxysterol-induced proinflammatory cytokine cascade in human macrophages: inhibition of NF-κB nuclear binding and increase in PPARγ expression

Palozza, Paola; Simone, Rossella Emanuela; Catalano, Alfonso; Monego, Giovanni; Barini, Angelina; Mele, Maria Cristina; Parrone, Nadia; Trombino, Sonia; Picci, Nevio; Ranelletti, Franco O.

doi:10.1016/j.jnutbio.2010.02.003

Cited by 106 publications

(78 citation statements)

References 65 publications

(68 reference statements)

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“…We observed increased translocation of the Ser536 phosphorylated p65 NF-kB subunit from the cytoplasm to the nucleus following treatment with LPS, 25-OHC and 7-ketoC. This is in agreement with a previous study showing that the same oxysterols promote NF-kB binding activity (Palozza et al, 2010), and is consistent with a TLR4-mediated inflammatory response. Furthermore, an increase in phospho-p65 staining was also observed following oxysterol and LPS treatments.…”

Section: Discussionsupporting

confidence: 93%

“…The oxysterols 25-OHC and 7-ketoC have previously been shown to promote proinflammatory cytokine expression in non-gestational tissues at concentrations ranging from 0.8 to 30 mg/ml (Dugas et al, 2010;Palozza et al, 2010). Due to this variability amongst different cell types, we sought to test a variety of concentrations to assess their effects on inflammation in trophoblasts.…”

Section: -Ohc and 7-ketoc Promote Proinflammatory Cytokine Productimentioning

confidence: 99%

“…; MIP, macrophage inflammatory protein-1b; TNF-a, tumour necrosis factor-a. (Valenzuela et al, 2003), also induce inflammation in a variety of cell types (Dugas et al, 2010;Palozza et al, 2010), although the mechanism of cellular inflammatory activation is unclear. Oxidized LDL (oxLDL) particles which carry these oxysterols also produce proinflammatory effects which, at least in macrophages, may involve the activation of TLR2 and TLR4 (Chavez-Sanchez et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF- B

Aye

Waddell

Mark

et al. 2012

Molecular Human Reproduction

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Oxidized cholesterol metabolites (oxysterols) promote inflammation in a variety of cell types and are thought to be involved in a number of disease pathologies. Oxysterol concentrations are increased in pregnancy, together with systemic oxidative stress and inflammation. We tested the hypothesis that oxysterols 25-hydroxycholesterol (25-OHC) and 7-ketocholesterol (7-ketoC) promote placental trophoblast inflammation, and determined the mechanisms involved. Treatment of primary trophoblasts in culture with 25-OHC and 7-ketoC increased the production of proinflammatory cytokines (interleukin-6, macrophage inflammatory protein-1b and tumour necrosis factor-a) in a concentration-dependent fashion. Inhibition of TLR4 activation using selective inhibitors of TLR4 complex formation (OxPAPC) or signalling transmission (CLI095) prevented lipopolysaccharide (LPS)-and oxysterol-induced inflammatory cytokine production. Pretreatment of trophoblasts with selective inhibitors of I-kB kinase activity (parthenolide and TPCA-1) reduced oxysterol-and LPS-stimulated inflammatory responses, consistent with the involvement of the nuclear factor kappa B (NF-kB) pathway downstream of TLR4 signalling. Both oxysterols also increased the phosphorylation and nuclear localization of NF-kB subunit p65/RelA. Oxysterols are also known to activate liver X receptors (LXRs) which can inhibit inflammatory signalling, either directly or indirectly via membrane cholesterol reduction. Treatment with the LXR agonist, T0901317, exerted significant anti-inflammatory effects, reducing LPS-and oxysteroldriven cytokine production. Treatment with methyl-b-cyclodextrin to deplete membrane microdomain cholesterol and thereby disrupt TLR4 signalling, similarly abrogated their effects. Together, these findings indicate that although oxysterols likely activate both pro-and anti-inflammatory pathways in the placenta, the predominant effect is the promotion of placental inflammation via TLR4-dependent activation of NF-kB.

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Section: Discussionsupporting

confidence: 93%

Section: -Ohc and 7-ketoc Promote Proinflammatory Cytokine Productimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF- B

Aye

Waddell

Mark

et al. 2012

Molecular Human Reproduction

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“…Lycopene protects the cell from lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant (8,9). In addition, lycopene exhibits other properties, including antiapoptosis (10), anti-inflammation (11,12), antiamyloid (13), anti-ischemia (14), and antitumor properties (15). Since lycopene has a high liposolubility, it can cross the blood-brain barrier (16).…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of lycopene pretreatment on transient global cerebral ischemia-reperfusion in rats: The role of the Nrf2/HO-1 signaling pathway

Lei

Zhang

et al. 2015

Molecular Medicine Reports

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Abstract. The present study aimed to investigate the neuroprotective effect of lycopene in a mouse model of bilateral common carotid artery occlusion (BCCAO) and the role of the Nrf2/HO-1 signaling pathway. A total of 60 male C57BL/6 mice, aged 12 weeks and weighing 20-24 g, were used in the present study. The mice were randomly assigned to three groups: Control, BCCAO and BCCAO + lycopene. The neurological score was assessed 24, 48 or 72 h following BCCAO. Hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were performed to detect neuronal death and survival. The production of glutathione (GSH) and reactive oxygen species were detected to investigate the oxidative stress. The expression levels of nuclear factor erythroid 2-related factor (Nrf2) and Heme oxygenase-1 (HO-1) were determined by western blotting. Lycopene significantly improved the neurological score in the BCCAO mice. It attenuated neuronal apoptosis, as indicated by TUNEL staining, and attenuated the oxidative stress induced by global ischemia. Lycopene increased the expression levels of Nrf2 and HO-1, indicating that the Nrf2/HO-1 signaling pathway may be involved in the neuroprotective effect of lycopene. The present study revealed that lycopene protects the brain from global ischemic injury, which is associated with its antiapoptotic effect and the activation of the Nrf2/HO-1 signaling pathway.

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“…These effects were associated with increased ROS production, through enhanced expression of NADPH oxidase; net posphorylation of MAPKs and NF-B activation also occurred [40].…”

mentioning

confidence: 96%

Inflammation-Related Gene Expression by Lipid Oxidation Derived Products in the Progression of Atherosclerosis

Poli¹,

Leonarduzzi²,

Gargiulo³

et al. 2010

Free Radical Biology and Medicine

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Lycopene prevention of oxysterol-induced proinflammatory cytokine cascade in human macrophages: inhibition of NF-κB nuclear binding and increase in PPARγ expression

Cited by 106 publications

References 65 publications

Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF- B

Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF- B

Neuroprotective effects of lycopene pretreatment on transient global cerebral ischemia-reperfusion in rats: The role of the Nrf2/HO-1 signaling pathway

Inflammation-Related Gene Expression by Lipid Oxidation Derived Products in the Progression of Atherosclerosis

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