Abstract
Background: Sarcoidosis is a systemic inflammatory disease characterized by noncaseating granulomas affecting many organs, especially the lungs and intrathoracic lymph nodes. Activated CD4+ T cells with a type 1 cytokine profile are considered to be of central importance for the pathogenesis. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that play important regulatory roles in numerous cellular processes, including inflammation. Three PPARs have been described, namely PPAR-alpha, -beta/delta and –gamma. They are expressed in many cell types, including macrophages and T cells. The purpose of this study was to investigate on the mRNA and protein level the expression of PPARs in lung cells of sarcoidosis patients.
Methods: Seventeen sarcoidosis patients and nine healthy controls underwent bronchoscopy with broncoalveolar lavage (BAL) whereafter CD4+ T cells and alveolar macrophages (AMs) were sorted by flow cytometry and subjected to real-time PCR analysis for mRNA expression of PPARs. Immunofluorescence staining of BAL cytospin slides with anti-PPAR antibodies was also performed.
Results: PPAR-alpha relative gene expression was significantly downregulated in CD4+ T cells of sarcoidosis patients, but no differences were observed with regard to T cell expression of the other PPARs. PPAR expression in AMs did not differ between patients and controls. No differences were observed between patients with or without Löfgren's syndrome.
Conclusion: The observed downregulation of PPAR-alpha in T helper cells may contribute to ongoing inflammation in pulmonary sarcoidosis via failure to repress proinflammatory genes.
- © 2011 ERS