PMID- 19700644
OWN - NLM
STAT- MEDLINE
DCOM- 20091110
LR  - 20211020
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 297
IP  - 5
DP  - 2009 Nov
TI  - The triterpenoid CDDO limits inflammation in preclinical models of cystic 
      fibrosis lung disease.
PG  - L828-36
LID - 10.1152/ajplung.00171.2009 [doi]
AB  - Excessive inflammation in cystic fibrosis (CF) lung disease is a contributor to 
      progressive pulmonary decline. Effective and well-tolerated anti-inflammatory 
      therapy may preserve lung function, thereby improving quality and length of life. 
      In this paper, we assess the anti-inflammatory effects of the synthetic 
      triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) in 
      preclinical models of CF airway inflammation. In our experiments, mice carrying 
      the R117H Cftr mutation have significantly reduced airway inflammatory responses 
      to both LPS and flagellin when treated with CDDO before inflammatory challenge. 
      Anti-inflammatory effects observed include reduced airway neutrophilia, reduced 
      concentrations of proinflammatory cytokines and chemokines, and reduced weight 
      loss. Our findings with the synthetic triterpenoids in multiple cell culture 
      models of CF human airway epithelia agree with effects previously described in 
      other disease models (e.g., neoplastic cells). These include the ability to 
      reduce NF-kappaB activation while increasing nuclear factor erythroid-related 
      factor 2 (Nrf2) activity. As these two signaling pathways appear to be pivotal in 
      regulating the net inflammatory response in the CF airway, these compounds are a 
      promising potential anti-inflammatory therapy for CF lung disease.
FAU - Nichols, David P
AU  - Nichols DP
AD  - Department of Pediatrics, National Jewish Health K1026, 1400 Jackson St., Denver, 
      CO 80206, USA. nicholsd@njhealth.org
FAU - Ziady, Assem G
AU  - Ziady AG
FAU - Shank, Samuel L
AU  - Shank SL
FAU - Eastman, Jean F
AU  - Eastman JF
FAU - Davis, Pamela B
AU  - Davis PB
LA  - eng
GR  - 5R0173870/PHS HHS/United States
GR  - P30-DK27651/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090821
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid)
RN  - 0 (Antioxidants)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-8)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Triterpenes)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
RN  - 12777-81-0 (Flagellin)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Bronchi/cytology
MH  - Bronchoalveolar Lavage
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Cystic Fibrosis/*complications/*prevention & control
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/antagonists & 
      inhibitors/metabolism
MH  - Disease Models, Animal
MH  - Epithelial Cells/drug effects/metabolism/pathology
MH  - Flagellin/administration & dosage/pharmacology
MH  - Humans
MH  - Inflammation/*complications/*prevention & control
MH  - Inflammation Mediators/metabolism
MH  - Interleukin-8/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - NF-E2-Related Factor 2/metabolism
MH  - NF-kappa B/metabolism
MH  - Neutrophils/cytology/drug effects
MH  - Oleanolic Acid/administration & dosage/*analogs & derivatives/pharmacology
MH  - Oxidation-Reduction/drug effects
MH  - Proteomics
MH  - Trachea/cytology
MH  - Triterpenes/administration & dosage/*pharmacology
PMC - PMC2777499
EDAT- 2009/08/25 09:00
MHDA- 2009/11/11 06:00
PMCR- 2010/11/01
CRDT- 2009/08/25 09:00
PHST- 2009/08/25 09:00 [entrez]
PHST- 2009/08/25 09:00 [pubmed]
PHST- 2009/11/11 06:00 [medline]
PHST- 2010/11/01 00:00 [pmc-release]
AID - 00171.2009 [pii]
AID - L-00171-2009 [pii]
AID - 10.1152/ajplung.00171.2009 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2009 Nov;297(5):L828-36. doi: 
      10.1152/ajplung.00171.2009. Epub 2009 Aug 21.