The prototypic long pentraxin 3 (PTX3) is a fluid phase pattern recognition receptor which plays non-redundant roles in the resistance against diverse pathogens, in the assembly of a hyaluronic acid-rich extracellular matrix and in female fertility. Inflammatory signals induce production of PTX3 in diverse cell types including myeloid dendritic cells (DC), fibroblasts and endothelial cells (EC). The present study was designed to explore the effect of glucocorticoid hormones (GC) on PTX3 production in different cellular contexts. In myeloid DC GC inhibited the PTX3 production. In contrast, in fibroblasts and EC GC alone induced and, under inflammatory conditions, enhanced and extended PTX3 production. In vivo administration of GC augmented the blood levels of PTX3 in mice and humans. Moreover, patients with Cushing's syndrome had increased levels of circulating PTX3 whereas PTX3 levels were decreased in subjects affected by iatrogenic hypocortisolism. In non-hematopoietic cells, GC receptor (GR) functioned as a ligand-dependent transcription factor (dimerization-dependent) to induce PTX3 gene expression. In contrast, in hematopoietic cells, GR repressed PTX3 gene transcription by interfering (dimerization-independent) with the action of other signaling pathways, likely NFKB and AP-1. Thus, divergent effects of GC were found to be due to different GR mechanisms. The results presented here indicate that GC have divergent effects on PTX3 production in hematopoietic (DC and macrophages) and non-hematopoietic (fibroblasts and EC) cells. The divergent effects of GC on PTX3 production is likely to reflect the different functions of this multifunctional molecule in innate immunity and in the construction of the extracellular matrix.
|Titolo:||Cell-specific regulation of PTX3 by glucocorticoid hormones in hematopoietic and non-hematopoietic cells|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
Settore MED/04 - Patologia Generale
Settore MED/08 - Anatomia Patologica
|Data di pubblicazione:||14-ago-2008|
|Digital Object Identifier (DOI):||10.1074/jbc.M805631200|
|Appare nelle tipologie:||01 - Articolo su periodico|