Peroxisome proliferator-activated receptor gamma as modulator of inflammation in pulmonary sarcoidosis

Abstract

Peroxisome proliferator-activated receptor (PPAR) includes the family of ligand-activated transcription factors which belong to the group of nuclear hormone receptors and are connected to retinoid, glucocorticoid and thyroid hormone receptors. There are three subtypes of PPARs: PPAR? (also known as NR1C3), PPAR? (known as NR1C1) and PPAR? (known as PPAR? or NR1C2). All of them take part in the metabolism, cell proliferation and immune response. PPAR? and PPAR? are identified as important immunomodulators and potentially represent an anti-inflammatory target for respiratory diseases. PPAR? deficiency in the lungs has been observed in the inflammatory diseases such as asthma, pulmonary alveolar proteinosis, fibrosis and sarcoidosis, as well as in the animal models of the lung inflammation. A small number of papers concerned with PPAR? in sarcoidosis point to the lowered activity of this factor in the alveolar macrophages and a lowered gene expression for the PPAR?, while the activity is preserved in healthy individuals. At the same time, an increased activity of the nuclear factor kappa B (NF-kB) in the bronchoalveolar lavage has been recorded in patients with sarcoidosis. The reason for the decrease in the production of PPAR? in sarcoidosis remains unknown. Several possible mechanisms are mentioned: genetic defect with lowered production, down-regulation due to the increased values of IFN-? or an increased decomposition of PPAR?. Further investigation will explain the mechanisms regarding the decreased production of PPAR? in sarcoidosis.