← Back to Search
Modulation Of Signalling Nuclear Factor-kappaB Activation Pathway By Polyphenols In Human Intestinal Caco-2 Cells.
Béatrice Romier, J. Van De Walle, Alexandrine During, Y. Larondelle, Y. Schneider
Published 2008 · Medicine, Biology
Download PDFAnalyze on Scholarcy
Recent studies support beneficial effects of polyphenols in various chronic inflammatory diseases, for example, the inflammatory bowel diseases. Inhibition of NF-kappaB activation by polyphenols could explain part of their anti-inflammatory properties, but few data are available on the intestine. The purpose of the present study was thus to investigate the effects of some polyphenols on NF-kappaB activation using human intestinal Caco-2 cells. Effects of standard polyphenols (50 mumol/l) were studied on different cellular events associated with NF-kappaB activation: (i) NF-kappaB activity using cells transiently transfected with a NF-kappaB-luciferase construct and stimulated by inflammatory agents (IL-1beta, TNF-alpha or lipopolysaccharides (LPS)); (ii) phosphorylation of the inhibitor of kappaB (IkappaB-alpha) analysed by Western blot; (iii) secretion of IL-8 quantified by ELISA assay. Results showed that chrysin and ellagic acid inhibited NF-kappaB activity, whereas genistein and resveratrol increased it. These effects were independent of the nature of the inducer, indicating that polyphenols may modulate NF-kappaB activation by acting on a common event to the cytokine- and LPS-mediated cascades. Chrysin strongly reduced (2.5-fold) IL-1beta-induced IkappaB-alpha phosphorylation, whereas ellagic acid increased it (1.7-fold). Ellagic acid, genistein and epigallocatechin gallate reduced (4- to 8-fold) IL-1beta-induced IL-8 secretion, while resveratrol promoted (1.7-fold) the secretion. Chrysin also diminished IL-8 secretion by 1.6-fold (but P>0.05). The data indicate that polyphenols can modulate the NF-kappaB activation pathway in the intestine. Chrysin could block NF-kappaB activation via the inhibition of IkappaB-alpha phosphorylation. The other molecular targets of the active polyphenols are still to be identified.
This paper references
Resveratrol attenuates TNF-α-induced activation of coronary arterial endothelial cells: role of NF-κB inhibition
A. Csiszár (2006)
Immunopathology of inflammatory digestive diseases
P Desreumaux (2004)
THE NF-κB AND IκB PROTEINS: New Discoveries and Insights
A. Baldwin (1996)
Chrysin suppresses lipopolysaccharide‐induced cyclooxygenase‐2 expression through the inhibition of nuclear factor for IL‐6 (NF‐IL6) DNA‐binding activity
Kyung Jin Woo (2005)
Genistein inhibits constitutive and inducible NFkappaB activation and decreases IL-8 production by human cystic fibrosis bronchial gland cells.
O. Tabary (1999)
Genistein prevents nuclear factor-kappa B activation and acute lung injury induced by lipopolysaccharide.
J. Kang (2001)
Inhibition of IL-8 production by green tea polyphenols in human nasal fibroblasts and A549 epithelial cells.
In-bae Kim (2006)
Naturally occurring NF-kB inhibitors
NH Nam (2006)
Immunologie du tube digestif et maladie de Crohn
P. Desreumaux (2004)
Antioxidants as novel therapy in a murine model of colitis.
H. Oz (2005)
Changes in the incidence of inflammatory bowel disease: what does it mean?
Modulatory Properties of Various Natural Chemopreventive Agents on the Activation of NF-κB Signaling Pathway
W. Jeong (2004)
Inhibition of ultraviolet B-mediated activation of nuclear factor κB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate
F. Afaq (2003)
Inhibition of NF-kB by dietary polyphenols leading to apoptosis and decrease of inflammation in human Caco-2 cells
B Romier (2006)
Hyperforin, the Active Component of St. John’s Wort, Induces IL-8 Expression in Human Intestinal Epithelial Cells Via a MAPK-Dependent, NF-κB-Independent Pathway
Changcheng Zhou (2004)
Dietary intake and bioavailability of polyphenols.
A. Scalbert (2000)
Inhibition of the transcription factor NF-kappa B by sesquiterpene lactones from Podachaenium eminens.
V. Castro (2000)
Polyphenols: food sources and bioavailability.
C. Manach (2004)
Comparative effects of polyphenols from green tea (EGCG) and soybean (genistein) on VEGF and IL-8 release from normal human keratinocytes stimulated with the proinflammatory cytokine TNFα
S. Trompezinski (2003)
Optimisation of hybridoma cell growth and monoclonal antibody secretion in a chemically defined, serum- and protein-free culture medium.
Y. Schneider (1989)
Curcumin blocks cytokine-mediated NF-kB kinase proinflammatory gene expression by inhibiting inhibitory factor I activity
C Jobin (1999)
Nuclear factor-kB: a pivotal transcription factor in chronic inflammatory diseases
PJ Barnes (1997)
20 years of NF-kappaB.
A. Chariot (2006)
Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.
P. Barnes (1997)
The IκB/NF-κB system: a key determinant of mucosal inflammation and protection
C. Jobin (2000)
Naturally occurring NF-kappaB inhibitors.
Nguyen-Hai Nam (2006)
In vivo quercitrin anti‐inflammatory effect involves release of quercetin, which inhibits inflammation through down‐regulation of the NF‐κB pathway
M. Comalada (2005)
The beginning of the end: IkB kinase (IKK) and NF-kB activation
M Karin (1999)
Green tea polyphenol extract attenuates colon injury induced by experimental colitis
E. Mazzon (2005)
Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD).
S. Shivananda (1996)
Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity.
C. Jobin (1999)
Epigallocatechin‐3‐gallate inhibits interleukin‐1β–induced expression of nitric oxide synthase and production of nitric oxide in human chondrocytes: Suppression of nuclear factor κB activation by degradation of the inhibitor of nuclear factor κB
R. Singh (2002)
Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation
P. Viatour (2005)
Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase.
M. Holmes-McNary (2000)
Indole-3-carbinol suppresses NF-κB and IκBα kinase activation, causing inhibition of expression of NF-κB-regulated antiapoptotic and metastatic gene products and enhancement of apoptosis in myeloid and leukemia cells
Y. Takada (2005)
20 Years of NFk B
A Chariot (2006)
Phosphorylation of NF-kB and IkB proteins: implications in cancer and inflammation
P Viatour (2005)
Caffeic acid phenethyl ester (CAPE) prevents inflammatory stress in organotypic hippocampal slice cultures.
P. Montpied (2003)
Molecular Targets of Dietary Polyphenols with Anti-inflammatory Properties
J. Yoon (2005)
Bacterial DNA evokes epithelial IL‐8 production by a MAPK‐dependent, NFκB‐independent pathway
M. Akhtar (2003)
Flavonoids inhibit tumor necrosis factor-alpha-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1) in respiratory epithelial cells through activator protein-1 and nuclear factor-kappaB: structure-activity relationships.
C. Chen (2004)
The Beginning of the End: IκB Kinase (IKK) and NF-κB Activation*
M. Karin (1999)
Quercetin, a bioflavonoid, inhibits the induction of interleukin 8 and monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha in cultured human synovial cells.
M. Sato (1997)
Resveratrol Suppresses TNF-Induced Activation of Nuclear Transcription Factors NF-κB, Activator Protein-1, and Apoptosis: Potential Role of Reactive Oxygen Intermediates and Lipid Peroxidation1
S. Manna (2000)
Overexpression of cytochrome P450 CYP2J2 protects against hypoxia-reoxygenation injury in cultured bovine aortic endothelial cells.
B. Yang (2001)
The flavonoid luteolin prevents lipopolysaccharide‐induced NF‐κB signalling and gene expression by blocking IκB kinase activity in intestinal epithelial cells and bone‐marrow derived dendritic cells
J. Kim (2005)
NF-idBSubunit-Specific Regulation ofthe Interleukin-8 Promoter
C. Kunsch (1993)
Bradykinin stimulates IL-6 and IL-8 production by human lung fibroblasts through ERK- and p38 MAPK-dependent mechanisms.
R. Hayashi (2000)
Differential cytokine expression by human intestinal epithelial cell lines: regulated expression of interleukin 8.
L. Eckmann (1993)
Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells.
Y. Li (2005)
Polyphenols and gastrointestinal diseases
G. Dryden (2006)
Polyphenols in the treatment of inflammatory bowel disease and acute pancreatitis
H. Shapiro (2006)
IFN-α Suppresses Activation of Nuclear Transcription Factors NF-κB and Activator Protein 1 and Potentiates TNF-Induced Apoptosis1
S. Manna (2000)
Chronic inflammatory bowel disease and cancer.
C. Pohl (2000)
Recent trends in the epidemiology of inflammatory bowel diseases: up or down?
P. Lakatos (2006)
[Molecular mechanism of interleukin-8 gene expression].
N. Mukaida (1998)
Factor VIIa Induces Tissue Factor-dependent Up-regulation of Interleukin-8 in a Human Keratinocyte Line*
Xiaolin Wang (2002)
The Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate Blocks Nuclear Factor-κB Activation by Inhibiting IκB Kinase Activity in the Intestinal Epithelial Cell Line IEC-6
F. Yang (2001)
Protein measurement with the Folin phenol reagent.
O. H. Lowry (1951)
Alterations in Receptor Expression or Agonist Concentration Change the Pathways Gastrin-Releasing Peptide Receptor Uses to Regulate Extracellular Signal-Regulated Kinase
Pei-Wen Chen (2004)
NF-kappa B subunit-specific regulation of the interleukin-8 promoter.
C. Kunsch (1993)
The regulation and functional consequence of proinflammatory cytokine binding on human intestinal epithelial cells.
A. Panja (1998)
This paper is referenced by
Guanylate cyclase-C signaling pathway regulates intestinal inflammatory injury and epithelial barrier function in Caco-2 cells
Y. Wang (2016)
Cocoa polyphenols prevent inflammation in the colon of azoxymethane-treated rats and in TNF-α-stimulated Caco-2 cells.
I. Rodríguez-Ramiro (2013)
Administration of Reconstituted Polyphenol Oil Bodies Efficiently Suppresses Dendritic Cell Inflammatory Pathways and Acute Intestinal Inflammation
E. Cavalcanti (2014)
Extraction and analysis of antioxidant capacity in rice bran extracts from different Sarawak local rice varieties
Tan Wen (2015)
An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances.
M. Zeinali (2017)
In vitro modulation of ABCB1/P-glycoprotein expression by polyphenols from Mangifera indica.
E. Chieli (2010)
The inhibitory effects of Gelam honey and its extracts on nitric oxide and prostaglandin E(2) in inflammatory tissues.
M. Kassim (2010)
Modulation of inflammatory mediators by Opuntia ficus-indica and Prunus avium bioproducts using an in vitro cell-based model of intestinal inflammation
Sara L. Nunes (2011)
Anti-inflammatory and Cytotoxic Activities of Mango (Mangifera indica L. var Keitt) Polyphenols in Cancer and Non-cancer Breast Fibroblasts in Vitro
Shirley Arbizu Berrocal (2013)
Cloudberry (Rubus chamaemorus) and its components as chemopreventive constituents in ApcMin mice and human colon adenocarcinoma cells
Essi Päivärinta (2017)
Nutrition, Well-Being and Health
J. Bouayed (2012)
Chemistry around imidazopyrazine and ibuprofen: discovery of novel fatty acid amide hydrolase (FAAH) inhibitors.
Frédéric De Wael (2010)
Whole Grain Consumption and Health of the Lower Gastrointestinal Tract: A Focus on Insoluble-Bound Phenolic Compounds
N. Okarter (2012)
Carotenoid exposure of Caco-2 intestinal epithelial cells did not affect selected inflammatory markers but altered their proteomic response.
Anouk Kaulmann (2012)
Anti-Inflammatory Nutrition as a Pharmacological Approach to Treat Obesity
B. Sears (2011)
Chrysin promotes tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induced apoptosis in human cancer cell lines.
X. Li (2011)
Green Tea Polyphenols and Gut Health
T. Rao (2013)
Synergistic anti-inflammatory effects and mechanisms of combined phytochemicals.
L. Zhang (2019)
MODULATION OF HOST INNATE IMMUNITY BY HEALTH-PROMOTING BACTERIA AND DIETARY COMPOUNDS
Valentina Taverniti (2013)
The O-methylation of chrysin markedly improves its intestinal anti-inflammatory properties: Structure-activity relationships of flavones.
Alexandrine During (2013)
New Insights toward Colorectal Cancer Chemotherapy Using Natural Bioactive Compounds
S. Redondo-Blanco (2017)
Phenolic Compounds in Poorly Represented Mediterranean Plants in Istria: Health Impacts and Food Authentication
Ana Miklavčič Višnjevec (2020)
The effects of pomegranate peel extract on recurrent aphthous stomatitis
S. Darakhshan (2019)
A systematic determination of polyphenols constituents and cytotoxic ability in fruit parts of pomegranates derived from five Chinese cultivars
R. Li (2016)
UNIVERSIDADE FEDERAL DE SANTA CATARINA DEPARTAMENTO DE FARMACOLOGIA
R. C. Schwanke (2012)
Bioactivity of Polyphenols: Preventive and Adjuvant Strategies toward Reducing Inflammatory Bowel Diseases—Promises, Perspectives, and Pitfalls
Anouk Kaulmann (2016)
Pomegranate polyphenolics reduce inflammation and ulceration in intestinal colitis-involvement of the miR-145/p70S6K1/HIF1α axis in vivo and in vitro.
Hyemee Kim (2017)
Progress in Drug and Formulation development for Chemoprevention of Oral Squamous Cell Carcinoma: A review.
H. Sarma (2019)
More citations, but a fall in impact factor.
P. Calder (2011)
Pharmacological oils for identification to target Inflammatory
D. Ciências (2012)
Better Living through Chemistry: Caloric Restriction (CR) and CR Mimetics Alter Genome Function to Promote Increased Health and Lifespan
Zoe E. Gillespie (2016)
Immunomodulatory effect of a wild blueberry anthocyanin-rich extract in human Caco-2 intestinal cells.
Valentina Taverniti (2014)See more