title: Cell-specific regulation of PTX3 by glucocorticoid hormones in hematopoietic and nonhematopoietic cells.
abstract: PTX3 (prototypic long pentraxin 3) is a fluid phase pattern recognition receptor, which plays nonredundant 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 syndrome had increased levels of circulating PTX3, whereas PTX3 levels were decreased in subjects affected by iatrogenic hypocortisolism. In nonhematopoietic 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, probably NFkappaB 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 nonhematopoietic (fibroblasts and EC) cells. The divergent effects of GC on PTX3 production probably reflect the different functions of this multifunctional molecule in innate immunity and in the construction of the extracellular matrix.
authors.affiliation: Istituto Clinico Humanitas, Istituto Di Ricerca Cura a Caratte Re Scientifico, Department of Immunology and Inflammation, Rozzano, Milan, Italy. andrea.doni@humanitas.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Doni
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mantovani
authors.forename: Chiara
authors.initials: C
authors.lastname: Porta
authors.forename: Jan
authors.initials: J
authors.lastname: Tuckermann
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
authors.forename: Anna
authors.initials: A
authors.lastname: Kleiman
authors.forename: Marina
authors.initials: M
authors.lastname: Sironi
authors.forename: Luca
authors.initials: L
authors.lastname: Rubino
authors.forename: Fabio
authors.initials: F
authors.lastname: Pasqualini
authors.forename: Manuela
authors.initials: M
authors.lastname: Nebuloni
authors.forename: Stefano
authors.initials: S
authors.lastname: Signorini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Peri
authors.forename: Antonio
authors.initials: A
authors.lastname: Sica
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Barbara
authors.initials: B
authors.lastname: Bottazzi
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007107:Immune System; D008024:Ligands; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D014158:Transcription, Genetic; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D005938:Glucocorticoids; D008024:Ligands; D000683:Serum Amyloid P-Component; D000099153:Pentraxins