Delayed activation of PPARγ by LPS and IFN‐γ attenuates the oxidative burst in macrophages
| Autor: | Brüne Bernhard, Knethen Andreas Von |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Lipopolysaccharides
Cell Survival medicine.drug_class medicine.medical_treatment Receptors Cytoplasmic and Nuclear Transfection Microbodies Biochemistry Monocytes Anti-inflammatory Cell Line Rosiglitazone Sepsis Interferon-gamma Mice Genes Reporter Escherichia coli Genetics medicine Animals Humans Hypoglycemic Agents Luciferases Molecular Biology Cells Cultured Respiratory Burst Desensitization (medicine) Chemistry Macrophages medicine.disease Recombinant Proteins Respiratory burst Thiazoles NG-Nitroarginine Methyl Ester Pyrimidines Immunology Tetradecanoylphorbol Acetate Thiazolidinediones Transcription Factors Biotechnology |
| Zdroj: | The FASEB Journal. 15:535-544 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.00-0187com |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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