Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder ch
Background PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods PPAR&#945;, &#946; and &#947; mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPAR&#945; protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPAR&#945; was analyzed by gel shift assay. Results In lymphocytes, the expression of PPAR&#945; mRNA, but not of PPAR&#946;, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPAR&#945; was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPAR&#945; and PPAR&#946; mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPAR&#947; mRNA levels were below the detection limit. Conclusion Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPAR&#945; may therefore contribute to the inflammatory processes that are observed in CF.
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Metadaten
Author:Veerle Reynders, Stefan Loitsch, Constanze Steinhauer, Thomas Wagner, Dieter Steinhilber, Joachim Bargon
URN:urn:nbn:de:hebis:30-31407
Document Type:Article
Language:English
Date of Publication (online):2006/09/15
Year of first Publication:2006
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2006/09/15
Note:
Copyright © 2006 Reynders et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 
Source:Respiratory Research 2006; 7(1): 104. doi: 10.1186/1465-9921-7-104.
HeBIS PPN:189981261
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 2.0

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