PMID- 21765824
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20111110
LR  - 20211020
IS  - 1687-4765 (Electronic)
IS  - 1687-4757 (Print)
VI  - 2011
DP  - 2011
TI  - Electrophilic PPARgamma Ligands Attenuate IL-1beta and Silica-Induced Inflammatory 
      Mediator Production in Human Lung Fibroblasts via a PPARgamma-Independent Mechanism.
PG  - 318134
LID - 10.1155/2011/318134 [doi]
LID - 318134
AB  - Acute and chronic lung inflammation is associated with numerous important disease 
      pathologies including asthma, chronic obstructive pulmonary disease and 
      silicosis. Lung fibroblasts are a novel and important target of anti-inflammatory 
      therapy, as they orchestrate, respond to, and amplify inflammatory cascades and 
      are the key cell in the pathogenesis of lung fibrosis. Peroxisome 
      proliferator-activated receptor gamma (PPARgamma) ligands are small molecules that 
      induce anti-inflammatory responses in a variety of tissues. Here, we report for 
      the first time that PPARgamma ligands have potent anti-inflammatory effects on human 
      lung fibroblasts. 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO) and 
      15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) inhibit production of the 
      inflammatory mediators interleukin-6 (IL-6), monocyte chemoattractant protein-1 
      (MCP-1), COX-2, and prostaglandin (PG)E(2) in primary human lung fibroblasts 
      stimulated with either IL-1beta or silica. The anti-inflammatory properties of these 
      molecules are not blocked by the PPARgamma antagonist GW9662 and thus are largely 
      PPARgamma independent. However, they are dependent on the presence of an 
      electrophilic carbon. CDDO and 15d-PGJ(2), but not rosiglitazone, inhibited NF-kappaB 
      activity. These results demonstrate that CDDO and 15d-PGJ(2) are potent 
      attenuators of proinflammatory responses in lung fibroblasts and suggest that 
      these molecules should be explored as the basis for novel, targeted 
      anti-inflammatory therapies in the lung and other organs.
FAU - Hogan, Christopher M
AU  - Hogan CM
AD  - Division of Pulmonary and Critical Care Medicine, University of Rochester, 601 
      Elmwood Avenue, P.O. Box 692, Rochester, NY 14642, USA.
FAU - Thatcher, Thomas H
AU  - Thatcher TH
FAU - Sapinoro, Ramil E
AU  - Sapinoro RE
FAU - Gurell, Michael N
AU  - Gurell MN
FAU - Ferguson, Heather E
AU  - Ferguson HE
FAU - Pollock, Stephen J
AU  - Pollock SJ
FAU - Jones, Carolyn
AU  - Jones C
FAU - Phipps, Richard P
AU  - Phipps RP
FAU - Sime, Patricia J
AU  - Sime PJ
LA  - eng
GR  - R01 EY017123/EY/NEI NIH HHS/United States
GR  - P30 ES001247/ES/NIEHS NIH HHS/United States
GR  - TL1 RR024135/RR/NCRR NIH HHS/United States
GR  - R01 ES007026/ES/NIEHS NIH HHS/United States
GR  - R03 HL095402/HL/NHLBI NIH HHS/United States
GR  - R01 HL075432/HL/NHLBI NIH HHS/United States
GR  - T32 ES007026/ES/NIEHS NIH HHS/United States
GR  - T32 HL066988/HL/NHLBI NIH HHS/United States
GR  - R01 EY015836/EY/NEI NIH HHS/United States
GR  - T32 HL007152/HL/NHLBI NIH HHS/United States
GR  - R01 DE011390/DE/NIDCR NIH HHS/United States
PT  - Journal Article
DEP - 20110616
PL  - United States
TA  - PPAR Res
JT  - PPAR research
JID - 101269101
PMC - PMC3135061
EDAT- 2011/07/19 06:00
MHDA- 2011/07/19 06:01
PMCR- 2011/06/16
CRDT- 2011/07/19 06:00
PHST- 2010/11/23 00:00 [received]
PHST- 2011/03/04 00:00 [revised]
PHST- 2011/03/25 00:00 [accepted]
PHST- 2011/07/19 06:00 [entrez]
PHST- 2011/07/19 06:00 [pubmed]
PHST- 2011/07/19 06:01 [medline]
PHST- 2011/06/16 00:00 [pmc-release]
AID - 10.1155/2011/318134 [doi]
PST - ppublish
SO  - PPAR Res. 2011;2011:318134. doi: 10.1155/2011/318134. Epub 2011 Jun 16.