Document Detail


Delayed activation of PPARgamma by LPS and IFN-gamma attenuates the oxidative burst in macrophages.
MedLine Citation:
PMID:  11156969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Desensitization of macrophages is important during the development of sepsis. It was our intention to identify mechanisms that promote macrophage deactivation upon contact with endotoxin (LPS) and interferon-gamma (IFN-gamma) in vitro. Macrophage activation was achieved with 12-O-tetradecanoylphorbol 13-acetate (TPA), and the oxidative burst (i.e., oxygen radical formation) was followed by oxidation of the redox-sensitive dyes hydroethidine and dichlorodihydrofluorescein diacetate. Prestimulation of macrophages for 15 h with a combination of LPS/IFN-gamma attenuated oxygen radical formation in response to TPA. Taking the anti-inflammatory properties of the peroxisome proliferator-activating receptorgamma (PPARgamma) into consideration, we established activation of PPARgamma in response to LPS/IFN-gamma by an electrophoretic mobility shift, supershift, and a reporter gene assay. The reporter contains a triple PPAR-responsive element (PPRE) in front of a thymidine kinase minimal promoter driving the luciferase gene. We demonstrated that PPRE decoy oligonucleotides, supplied in front of LPS/IFN-gamma, allowed a full oxidative burst to recover upon TPA addition. Furthermore, we suppressed the oxidative burst by using the PPARgamma agonists 15-deoxy-Delta12,14-prostaglandin J2, BRL 49653, or ciglitazone. No effect was observed with WY 14643, a PPARalpha agonist. We conclude that activation of PPARs, most likely PPARgamma, promotes macrophage desensitization, thus attenuating the oxidative burst. This process appears important during development of sepsis.
Authors:
A Von Knethen A; B Brüne
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  15     ISSN:  0892-6638     ISO Abbreviation:  FASEB J.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-03-22     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  535-44     Citation Subset:  IM    
Affiliation:
Department of Medicine IV-Experimental Division, University of Erlangen-Nürnberg, Faculty of Medicine, 91054 Erlangen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Survival / drug effects
Cells, Cultured
Escherichia coli
Genes, Reporter
Humans
Hypoglycemic Agents / pharmacology
Interferon-gamma / pharmacology*
Lipopolysaccharides / pharmacology*
Luciferases / genetics
Macrophages / cytology,  drug effects,  physiology*
Mice
Microbodies / drug effects,  physiology
Monocytes / cytology*,  drug effects
NG-Nitroarginine Methyl Ester / pharmacology
Pyrimidines / pharmacology
Receptors, Cytoplasmic and Nuclear / agonists,  physiology*
Recombinant Proteins
Respiratory Burst / drug effects,  physiology*
Tetradecanoylphorbol Acetate / pharmacology
Thiazoles / pharmacology
Thiazolidinediones*
Transcription Factors / agonists,  physiology*
Transfection
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Lipopolysaccharides; 0/Pyrimidines; 0/Receptors, Cytoplasmic and Nuclear; 0/Recombinant Proteins; 0/Thiazoles; 0/Thiazolidinediones; 0/Transcription Factors; 122320-73-4/rosiglitazone; 16561-29-8/Tetradecanoylphorbol Acetate; 50892-23-4/pirinixic acid; 50903-99-6/NG-Nitroarginine Methyl Ester; 74772-77-3/ciglitazone; 82115-62-6/Interferon-gamma; EC 1.13.12.-/Luciferases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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