PMID- 20008283
OWN - NLM
STAT- MEDLINE
DCOM- 20101110
LR  - 20201209
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Linking)
VI  - 43
IP  - 5
DP  - 2010 Nov
TI  - 17,18-epoxyeicosatetraenoic acid targets PPARgamma and p38 mitogen-activated protein 
      kinase to mediate its anti-inflammatory effects in the lung: role of soluble 
      epoxide hydrolase.
PG  - 564-75
LID - 10.1165/rcmb.2009-0155OC [doi]
AB  - This study sought to assess putative pathways involved in the anti-inflammatory 
      effects of 17,18-epoxyeicosatetraenoic acid (17,18-EpETE), as measured by a 
      decrease in the contractile reactivity and Ca(2+) sensitivity of TNF-alpha-pretreated 
      human bronchi. Tension measurements performed in the presence of 
      12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a soluble epoxide hydrolase 
      (sEH)-specific inhibitor, demonstrated that 17,18-EpETE reduced the reactivity of 
      TNF-alpha-pretreated tissues. The overexpression of sEH detected in patients with 
      asthma and TNF-alpha-treated bronchi contributed to the maintenance of 
      hyperresponsiveness in our models, which involved intracellular proinflammatory 
      cascades. The inhibition of peroxisome proliferator-activated receptor (PPAR)gamma by 
      GW9662 abolished 17,18-EpETE + AUDA-mediated anti-inflammatory effects by 
      inducing IkappaBalpha degradation and cytokine synthesis, indicating that PPARgamma is a 
      molecular target of epoxy-eicosanoids. Western blot analysis revealed that 
      17,18-EpETE pretreatment reversed the phosphorylation of p38 mitogen-activated 
      protein kinase (p38-MAPK) induced by TNF-alpha in human bronchi. The Ca(2+) 
      sensitivity of human bronchial explants was also quantified on beta-escin 
      permeabilized preparations. The presence of SB203580, a p38-MAPK inhibitor, 
      reversed the effect induced by epoxy-eicosanoid in the presence of AUDA on 
      TNF-alpha-triggered Ca(2+) hypersensitivity by increasing the phosphorylation level 
      of PKC Potentiated Inhibitor Protein-17 (CPI-17) regulatory protein. Moreover, 
      PPARgamma ligands, such as rosiglitazone and 17,18-EpETE, decreased the expression of 
      CPI-17, both at the mRNA and protein levels, whereas this effect was countered by 
      GW9662 treatment in TNF-alpha-treated bronchi. These results demonstrate that 
      17,18-EpETE is a potent regulator of human lung inflammation and concomitant 
      hyperresponsiveness, and may represent a valuable asset against critical 
      inflammatory bronchial disorder.
FAU - Morin, Caroline
AU  - Morin C
AD  - Le Bilarium, Department of Physiology and Biophysics, Faculty of Medicine and 
      Health Sciences, Universite de Sherbrooke, Sherbrooke, Quebec,, J1H 5N4 Canada.
FAU - Sirois, Marco
AU  - Sirois M
FAU - Echave, Vincent
AU  - Echave V
FAU - Albadine, Roula
AU  - Albadine R
FAU - Rousseau, Eric
AU  - Rousseau E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091211
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Arachidonic Acids)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Muscle Proteins)
RN  - 0 (PPAR gamma)
RN  - 0 (PPP1R14A protein, human)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 131339-23-6 (17,18-epoxy-5,8,11,14-eicosatetraenoic acid)
RN  - 81276-03-1 (14,15-epoxy-5,8,11-eicosatrienoic acid)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.53 (Myosin-Light-Chain Phosphatase)
RN  - EC 3.1.3.53 (PPP1R12A protein, human)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - FC398RK06S (8,11,14-Eicosatrienoic Acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 8,11,14-Eicosatrienoic Acid/analogs & derivatives/pharmacology
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Arachidonic Acids/antagonists & inhibitors/*pharmacology
MH  - Bronchi/drug effects/enzymology/pathology
MH  - Calcium/pharmacology
MH  - Cyclooxygenase 2/metabolism
MH  - Epoxide Hydrolases/*metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Lung/drug effects/enzymology/*pathology
MH  - Models, Biological
MH  - Muscle Proteins
MH  - Myosin-Light-Chain Phosphatase/metabolism
MH  - PPAR gamma/antagonists & inhibitors/*metabolism
MH  - Phosphoprotein Phosphatases/metabolism
MH  - Phosphorylation/drug effects
MH  - Pneumonia/*enzymology/pathology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Solubility/drug effects
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
EDAT- 2009/12/17 06:00
MHDA- 2010/11/11 06:00
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/11/11 06:00 [medline]
AID - 2009-0155OC [pii]
AID - 10.1165/rcmb.2009-0155OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2010 Nov;43(5):564-75. doi: 10.1165/rcmb.2009-0155OC. 
      Epub 2009 Dec 11.