title: Synergistic induction of thymic stromal lymphopoietin by tumor necrosis factor alpha and Th2 cytokine in nasal polyp fibroblasts.
abstract: BACKGROUND
  Thymic stromal lymphopoietin (TSLP) is elevated in airway inflammatory diseases such as asthma and triggers dendritic cell-mediated activation of Th2 inflammatory responses. Although allergic chronic sinusitis is a Th2 inflammatory disease of the upper airway, the mechanism underlying the predominance of Th2 responses still has to be clarified. We investigated the expression of TSLP in cytokine-treated nasal polyp fibroblasts.
  
  
  METHODS
  Fibroblast lines were established from nasal polyp tissues. Their expression of TSLP mRNA was evaluated by real-time reverse-transcription polymerase chain reaction. The amount of TSLP in the supernatants was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Nasal polyp fibroblasts have the capacity to produce TSLP in response to stimulation by tumor necrosis factor (TNF) alpha. Combined stimulation with TNF-alpha + a Th2 cytokine (IL-4 or IL-13) was synergistic for TSLP production by the nasal polyp fibroblasts. This response was time and dose dependent. The TNF-alpha + Th2 cytokine (IL-4 or IL-13)-induced TSLP production was strongly inhibited by interferon gamma but not by IL-10.
  
  
  CONCLUSIONS
  These results suggest that nasal polyp fibroblasts play a role in the development and regulation of Th2-type inflammation in the upper airway by producing TSLP.
authors.affiliation: Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan. nonaka@nms.ac.jp
authors.forename: Manabu
authors.initials: M
authors.lastname: Nonaka
authors.forename: Akira
authors.initials: A
authors.lastname: Fukumoto
authors.forename: Nozomu
authors.initials: N
authors.lastname: Ogihara
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sakanushi
authors.forename: Ruby
authors.initials: R
authors.lastname: Pawankar
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yagi
mesh_terms: D001706:Biopsy; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007114:Immunization; D009298:Nasal Polyps; D012852:Sinusitis; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D000094632:Thymic Stromal Lymphopoietin