title: Differential cytokine profiles upon comparing selective versus classic glucocorticoid receptor modulation in human peripheral blood mononuclear cells and inferior turbinate tissue.
abstract: BACKGROUND
  Glucocorticoid Receptor agonists, particularly classic glucocorticoids, are the mainstay among treatment protocols for various chronic inflammatory disorders, including nasal disease. To steer away from steroid-induced side effects, novel GR modulators exhibiting a more favorable therapeutic profile remain actively sought after. Currently, the impact of 2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium chloride a plant-derived selective glucocorticoid receptor modulator named compound A, on cytokine production in ex vivo human immune cells and tissue has scarcely been evaluated.
  
  
  RESULTS
  The current study aimed to investigate the effect of a classic glucocorticoid versus compound A on cytokine and inflammatory mediator production after stimulation with Staphylococcus aureus-derived enterotoxin B protein in peripheral blood mononuclear cells (PBMCs) as well as in inferior nasal turbinate tissue. To this end, tissue fragments were stimulated with RPMI (negative control) or Staphylococcus aureus-derived enterotoxin B protein for 24 hours, in presence of solvent, or the glucocorticoid methylprednisolone or compound A at various concentrations. Supernatants were measured via multiplex for pro-inflammatory cytokines (IL-1β, TNFα) and T-cell- and subset-related cytokines (IFN-γ, IL-2, IL-5, IL-6, IL-10, and IL-17). In concordance with the previously described stimulatory role of superantigens in the development of nasal polyposis, a 24h Staphylococcus aureus-derived enterotoxin B protein stimulation induced a significant increase of IL-2, IL-1β, TNF-α, and IL-17 in PBMCs and in inferior turbinates and of IL-5 and IFN-γ in PBMCs.
  
  
  CONCLUSIONS
  Notwithstanding some differences in amplitude, the overall cytokine responses to methylprednisolone and compound A were relatively similar, pointing to a conserved and common mechanism in cytokine transrepression and anti-inflammatory actions of these GR modulators. Furthermore, these results provide evidence that selective glucocorticoid receptor modulator-mediated manipulation of the glucocorticoid receptor in human tissues, supports its anti-inflammatory potential.
authors: Laboratory of Experimental Cancer Research (LECR), Department of Radiation Oncology & Experimental Cancer Research, Ghent University, Gent, Belgium.
authors: Ilse M
authors: IM
authors: Beck
authors: Upper Airway Research Laboratory (URL), Ghent University Hospital, Ghent, Belgium.
authors: Koen
authors: K
authors: Van Crombruggen
authors: Upper Airway Research Laboratory (URL), Ghent University Hospital, Ghent, Belgium.
authors: Gabriele
authors: G
authors: Holtappels
authors: Laboratoire d'Innovation Thérapeutique, Unité Mixte de Recherche 7200, Centre National de la Recherche Scientifique-Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
authors: François
authors: F
authors: Daubeuf
authors: Laboratoire d'Innovation Thérapeutique, Unité Mixte de Recherche 7200, Centre National de la Recherche Scientifique-Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
authors: Nelly
authors: N
authors: Frossard
authors: Upper Airway Research Laboratory (URL), Ghent University Hospital, Ghent, Belgium; Division of ENT Diseases, Clintec, Karolinska Institute, Stockholm, Sweden.
authors: Claus
authors: C
authors: Bachert
authors: Receptor Research Laboratories, Nuclear Receptor Lab (NRL), VIB Department of Medical Protein Research, Ghent University, Gent, Belgium.
authors: Karolien
authors: K
authors: De Bosscher
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D014439:Tyramine / Q000031:analogs & derivatives / Q000494:pharmacology; D055815:Young Adult
chemical_list: C104564:2-(4-acetoxyphenyl)-2-chloro-N-methylethylamine; D000085:Acetates; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D008775:Methylprednisolone; D014439:Tyramine