title: Dexamethasone restrains ongoing expression of interleukin-23p19 in peripheral blood-derived human macrophages.
abstract: BACKGROUND
  Since its recent discovery, interleukin-23 has been shown to be involved in the pathogenesis of autoimmune diseases favoring the development of a T cell subset referred to as T helper 17. Glucocorticoids are widely employed in inflammatory and autoimmune diseases as they inhibit pro-inflammatory signaling and prevent production of inflammation mediators. Very limited information is available about the efficacy of synthetic glucocorticoids in containing the expression of interleukin-23 under cell activation.
  
  
  RESULTS
  We demonstrate here that the glucocorticoid analogue dexamethasone administered to human monocyte-derived macrophages is indeed able to restrain the expression of interleukin-23 once it has been triggered by a pro-inflammatory stimulus. This effect of dexamethasone is here demonstrated being secondary to suppression of p38 MAPK activity, and involving a protein phosphatase--likely MAPK phosphatase-1 (MKP-1).
  
  
  CONCLUSIONS
  Results reported in this paper show that a 10 nanomolar dose of dexamethasone not only prevents inflammatory activation but is also efficacious in confining active inflammation. This effect is here demonstrated not to occur through "canonical" inhibition of the NF-κB transcription factor but through a distinct cascade of down-modulation, that underlines the importance of the transactivating activity of glucocorticoid receptor in the context of its anti-inflammatory action.
authors.affiliation: Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Via A, Saffi 2, 61029 Urbino, PU, Italy. linda.palma@uniurb.it
authors.forename: Linda
authors.initials: L
authors.lastname: Palma
authors.forename: Carla
authors.initials: C
authors.lastname: Sfara
authors.forename: Antonella
authors.initials: A
authors.lastname: Antonelli
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
mesh_terms: D000328:Adult; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D053760:Interleukin-23 Subunit p19 / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D053760:Interleukin-23 Subunit p19; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D003907:Dexamethasone; D048051:p38 Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1