Cell-specific regulation of PTX3 by glucocorticoid hormones in hematopoietic and nonhematopoietic cells

Andrea Doni, Giovanna Mantovani, Chiara Porta, Jan Tuckermann, Holger M. Reichardt, Anna Kleiman, Marina Sironi, Luca Rubino, Fabio Pasqualini, Manuela Nebuloni, Stefano Signorini, Giuseppe Peri, Antonio Sica, Paolo Beck-Peccoz, Barbara Bottazzi, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review

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 NFκB 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.

Original languageEnglish
Pages (from-to)29983-29992
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number44
DOIs
Publication statusPublished - Oct 31 2008

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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