Enterodiol and enterolactone modulate the immune response by acting on nuclear factor-kappaB (NF-kappaB) signaling.
Lignan-rich whole-grain cereals, beans, berries, and nuts show protective effects against a variety of chronic diseases, including cancer. Lignans are converted by intestinal microflora to enterolactone (EL) and its oxidation product enterodiol (ED). To investigate the immunomodulatory effect of EL and ED in human cells, peripheral blood lymphocytes were treated with increasing physiologically relevant concentrations of EL and ED (0-1000 microM) and stimulated with lipopolysaccharide (LPS) and anti-CD3 plus anti-CD28 monoclonal antibodies. A dose-related inhibition of cell proliferation and cytokine production was observed, with EL being the most active. Molecular investigations in THP-1 cells showed that both EL and ED prevented inhibitory-kappaB (I-kappaB) degradation and nuclear factor-kappaB (NF-kappaB) activation, which in turn resulted in decreased tumor necrosis factor-alpha (TNF-alpha) production. EL and ED were also able to pass the intestinal barrier and modulate cytokine production. The findings of the present study reveal potential mechanisms that could explain some in vivo beneficial effects of lignans.
Corsini
Emanuela
E
Laboratory of Toxicology, Department of Pharmacological Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy. emanuela.corsini@unimi.it
Dell'Agli
Mario
M
Facchi
Alessandra
A
De Fabiani
Emma
E
Lucchi
Laura
L
Boraso
Maria Serena
MS
Marinovich
Marina
M
Galli
Corrado L
CL
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology*; D017705:Lignans / Q000276:immunology / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D007155:Immunologic Factors; D017705:Lignans; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone