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Omega-3 docosahexaenoic acid and procyanidins inhibit cyclooxygenase activity and attenuate NF-κB activation through a p105/p50 regulatory mechanism in macrophage inflammation.
MedLine Citation:
PMID:  21954853     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The inflammatory response has been implicated in the pathogenesis of many chronic diseases. Along these lines, the modulation of inflammation by consuming bioactive food compounds, such as ω-3 fatty acids or procyanidins, is a powerful tool to promote good health. In this study, the administration of docosahexaenoic acid (DHA) and B1, B2 and C1 procyanidins, alone or in combination, prevented the inflammatory response induced by LPS endotoxin in human macrophages and brought them to the homeostatic state. DHA and B1 were strong and selective negative regulators of cyclooxygenase 1 activity, with IC50 values of 13.5 μM and 8.0 μM, respectively. Additionally, B2 and C1 were selective inhibitors of pro-inflammatory cyclooxygenase 2 activity, with IC50 values of 9.7 μM and 3.3 μM, respectively. Moreover, DHA and pure procyanidins prevented the activation of the nuclear factor kappa B (NF-κB) cascade at both early and late stages with shared mechanisms. These included inhibiting IκB-α phosphorylation, inducing the cytoplasmic retention of pro-inflammatory NF-κB proteins through p105 (NF-κB1) over-expression, favouring the nuclear translocation of the p50:p50 transcriptional repressor homodimer instead of the p50:p65 pro-inflammatory heterodimer, inhibiting binding of NF-κB DNA to κB sites and, finally, decreasing the release of NF-κB-regulated cytokines and prostaglandins. In conclusion, DHA and pure procyanidins are strong and selective inhibitors of cyclooxygenase activity and NF-κB activation through a p105/p50-dependent regulatory mechanism.
Authors:
Neus Martinez-Micaelo; Noemi González-Abuín; Ximena Terra; Cristobal Richart; Anna Ardèvol; Montserrat Pinent; Mayte Blay
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-28
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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