Procyanidin B2 inhibits inflammasome‐mediated IL‐1β production in lipopolysaccharide‐stimulated macrophages
2015
Martinez‐Micaelo, Neus | González‐Abuín, Noemi | Pinent, Montserrat | Ardévol, Anna | Blay, Mayte
SCOPE: 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. METHODS AND RESULTS: To determine the role of procyanidin B₂in 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 B₂mediated 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 B₂decreases 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. CONCLUSION: This study provides the first evidence that procyanidin B₂inhibits inflammasome activation and IL‐1β secretion during LPS‐induced acute inflammation in human macrophages.
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