Peroxisome Proliferator-Activated Receptor α PPARα down-regulation in cystic fibrosis lymphocytesReportar como inadecuado




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Respiratory Research

, 7:104

First Online: 30 July 2006Received: 16 February 2006Accepted: 30 July 2006

Abstract

BackgroundPPARs 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.

MethodsPPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay.

ResultsIn lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced -37%; p < 0.002 in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα 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 PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit.

ConclusionLymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF.

AbbreviationsAAArachidonic acid

AP-1Activator protein-1

CFCystic fibrosis

CFTRCystic fibrosis transmembrane conductance regulator

DHADocosahexaenoic acid

NF-κBNuclear factor-κB

PPARPeroxisome Proliferator-Activated Receptor

PPREPPAR response element

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Autor: Veerle Reynders - Stefan Loitsch - Constanze Steinhauer - Thomas Wagner - Dieter Steinhilber - Joachim Bargon

Fuente: https://link.springer.com/



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