PMID- 19649246
OWN - NLM
STAT- MEDLINE
DCOM- 20091110
LR  - 20220331
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 7
DP  - 2009 Jul 31
TI  - Punicic acid a conjugated linolenic acid inhibits TNFalpha-induced neutrophil 
      hyperactivation and protects from experimental colon inflammation in rats.
PG  - e6458
LID - 10.1371/journal.pone.0006458 [doi]
LID - e6458
AB  - BACKGROUND: Neutrophils play a major role in inflammation by releasing large 
      amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO). The 
      proinflammatory cytokine TNFalpha primes ROS production through phosphorylation 
      of the NADPH-oxidase subunit p47phox on Ser345. Conventional anti-inflammatory 
      therapies remain partially successful and may have side effects. Therefore, 
      regulation of neutrophil activation by natural dietary components represents an 
      alternative therapeutic strategy in inflammatory diseases such as inflammatory 
      bowel diseases. The aim of this study was to assess the effect of punicic acid, a 
      conjugated linolenic fatty acid from pomegranate seed oil on TNFalpha-induced 
      neutrophil hyperactivation in vitro and on colon inflammation in vivo. 
      METHODOLOGY AND PRINCIPAL FINDINGS: We analyzed the effect of punicic acid on 
      TNFalpha-induced neutrophil upregulation of ROS production in vitro and on 
      TNBS-induced rat colon inflammation. Results show that punicic acid inhibited 
      TNFalpha-induced priming of ROS production in vitro while preserving 
      formyl-methionyl-leucyl-phenylalanine (fMLP)-induced response. This effect was 
      mediated by the inhibition of Ser345-p47phox phosphorylation and upstream kinase 
      p38MAPK. Punicic acid also inhibited fMLP- and TNFalpha+fMLP-induced MPO 
      extracellular release from neutrophils. In vivo experiments showed that punicic 
      acid and pomegranate seed oil intake decreased neutrophil-activation and 
      ROS/MPO-mediated tissue damage as measured by F2-isoprostane release and 
      protected rats from TNBS-induced colon inflammation. CONCLUSIONS/SIGNIFICANCE: 
      These data show that punicic acid exerts a potent anti-inflammatory effect 
      through inhibition of TNFalpha-induced priming of NADPH oxidase by targeting the 
      p38MAPKinase/Ser345-p47phox-axis and MPO release. This natural dietary compound 
      may provide a novel alternative therapeutic strategy in inflammatory diseases 
      such as inflammatory bowel diseases.
FAU - Boussetta, Tarek
AU  - Boussetta T
AD  - INSERM, U773, Universite Paris, Faculte de Medecine, Paris, France.
FAU - Raad, Houssam
AU  - Raad H
FAU - Letteron, Philippe
AU  - Letteron P
FAU - Gougerot-Pocidalo, Marie-Anne
AU  - Gougerot-Pocidalo MA
FAU - Marie, Jean-Claude
AU  - Marie JC
FAU - Driss, Fathi
AU  - Driss F
FAU - El-Benna, Jamel
AU  - El-Benna J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090731
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Linolenic Acids)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (neutrophil cytosolic factor 1)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - VFQ03H211O (punicic acid)
SB  - IM
MH  - Animals
MH  - Colitis/*prevention & control
MH  - Linolenic Acids/*pharmacology
MH  - Lymphocyte Activation/*drug effects
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - NADPH Oxidases/metabolism
MH  - Neutrophils/*drug effects/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC2714468
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/08/04 09:00
MHDA- 2009/11/11 06:00
PMCR- 2009/07/31
CRDT- 2009/08/04 09:00
PHST- 2009/04/27 00:00 [received]
PHST- 2009/07/03 00:00 [accepted]
PHST- 2009/08/04 09:00 [entrez]
PHST- 2009/08/04 09:00 [pubmed]
PHST- 2009/11/11 06:00 [medline]
PHST- 2009/07/31 00:00 [pmc-release]
AID - 09-PONE-RA-10003R1 [pii]
AID - 10.1371/journal.pone.0006458 [doi]
PST - epublish
SO  - PLoS One. 2009 Jul 31;4(7):e6458. doi: 10.1371/journal.pone.0006458.