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Procyanidin B 2 inhibits inflammasome‐mediated IL‐1β production in lipopolysaccharide‐stimulated macrophages
Author(s) -
MartinezMicaelo Neus,
GonzálezAbuín Noemi,
Pinent Montserrat,
Ardévol Anna,
Blay Mayte
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201400370
Subject(s) - inflammasome , aim2 , secretion , chemistry , caspase 1 , lipopolysaccharide , inflammation , microbiology and biotechnology , biology , biochemistry , immunology , receptor
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 B 2 in inflammasome activation, LPS‐primed THP‐1‐macrophages were supplemented with or without procyanidin B 2 . Western blot analysis of COX 2 , 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 B 2 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 COX 2 , iNOS and production of IL‐6 and NO. Furthermore, procyanidin B 2 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. Conclusion This study provides the first evidence that procyanidin B 2 inhibits inflammasome activation and IL‐1β secretion during LPS‐induced acute inflammation in human macrophages.