Procyanidin B2 inhibits inflammasome-mediated IL-1β production in lipopolysaccharide-stimulated macrophages.
METHODS
Macrophage stimulation with bacterial LPS triggers inflammasome activation, resulting in pro-inflammatory IL-1β cytokine maturation and secretion. IL-1β underlies the pathologies of many diseases, including type-2 diabetes. Thus, the modulation of the inflammatory response through bioactive food compounds, such as procyanidins, is a powerful tool to promote homeostasis.


RESULTS
To determine the role of procyanidin B2 in inflammasome activation, LPS-primed THP-1-macrophages were supplemented with or without procyanidin B2 . Western blot analysis of COX2 , iNOS, p65, NLRP3 and IL-1β was performed followed by p65 supershift assay, in vivo caspase-1 activation assay and NO, IL-1β and IL-6 determination. Procyanidin B2 mediated inhibition of inflammasome activation includes the inactivation of the NF-κB signalling pathway, the first stage required for the transcription of inflammasome precursors, through the inhibition of p65 nuclear expression and DNA binding, resulting in the transcriptional repression of target genes, such as COX2 , iNOS and production of IL-6 and NO. Furthermore, procyanidin B2 decreases NLRP3 and pro-IL-1β cytoplasmic pools, limiting components of inflammasome activation and impeding inflammasome assembly and caspase-1 activation, and finally secretion of active IL-1β.


CONCLUSIONS
This study provides the first evidence that procyanidin B2 inhibits inflammasome activation and IL-1β secretion during LPS-induced acute inflammation in human macrophages.
Mobiofood Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, Tarragona, Spain.
Neus
N
Martinez-Micaelo
Noemi
N
González-Abuín
Montserrat
M
Pinent
Anna
A
Ardévol
Mayte
M
Blay
D044946:Biflavonoids / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D015398:Signal Transduction
D044946:Biflavonoids; D002352:Carrier Proteins; C508600:IL6 protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D044945:Proanthocyanidins; C479580:procyanidin B2; D009569:Nitric Oxide; D002392:Catechin; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020170:Caspase 1
B2; Inflammasome; LPS; Macrophages; NF-κB; Procyanidins; TLR4