title: Microbial superantigens induce glucocorticoid receptor beta and steroid resistance in a nasal explant model.
abstract: OBJECTIVE
  To study the role of superantigen (SAg) in inducing glucocorticoid (GC) receptor beta and steroid resistance in an explant model of nasal tissue.
  
  
  METHODS
  Nasal tissue was obtained from inferior turbinates of controls and ragweed (RW)-sensitive patients. Tissue samples were incubated with SAg of staphylococcal enterotoxin B. In addition, tissue samples from RW-sensitive patients were incubated with RW allergen in the presence and absence of both SAg and dexamethasone (DEX). The expression of GC receptor beta was assessed by immunocytochemistry. The expression of interleukin (IL)-2 and IL-4 mRNA was assessed by in situ hybridization.
  
  
  RESULTS
  SAg induced an increase in the expression of GC receptor beta in atopic tissue and to a lesser extent in nonatopic tissue. The most significant induction of GC receptor beta was observed in response to SAg and RW in atopic tissue. Stimulation of atopic tissue with RW alone and SAg alone induced IL-4 and IL-2 mRNA, respectively. Incubation of atopic tissue with both SAg and RW induced both IL-2 and IL-4 mRNA. The increase in IL-4 mRNA expression was blunted by the addition of DEX to atopic tissue stimulated with RW alone but not to tissue stimulated by both RW and SAg.
  
  
  CONCLUSIONS
  Our results demonstrate that SAgs induce steroid resistance in atopic nasal explant tissue by up-regulating the expression of GC receptor beta. Furthermore, we have shown that the up-regulation of GC receptor beta is a local event that is associated with the coexpression of IL-2 and IL-4 mRNA.
authors.affiliation: Department of Otolaryngology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Samer
authors.initials: S
authors.lastname: Fakhri
authors.forename: Meri
authors.initials: M
authors.lastname: Tulic
authors.forename: Pota
authors.initials: P
authors.lastname: Christodoulopoulos
authors.forename: Motonori
authors.initials: M
authors.lastname: Fukakusa
authors.forename: Saul
authors.initials: S
authors.lastname: Frenkiel
authors.forename: Donald Y M
authors.initials: DY
authors.lastname: Leung
authors.forename: Qutayba A
authors.initials: QA
authors.lastname: Hamid
mesh_terms: D031164:Ambrosia / Q000276:immunology; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D003907:Dexamethasone / Q000378:metabolism*; D004351:Drug Resistance / Q000187:drug effects*; D004768:Enterotoxins / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000276:immunology*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D018089:Superantigens / Q000276:immunology* / Q000494:pharmacology*; D014420:Turbinates / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D004768:Enterotoxins; D007376:Interleukin-2; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018089:Superantigens; C121943:glucocorticoid receptor beta; D015847:Interleukin-4; C031818:enterotoxin B, staphylococcal; D003907:Dexamethasone