Synergistic induction of thymic stromal lymphopoietin by tumor necrosis factor alpha and Th2 cytokine in nasal polyp fibroblasts.
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.
Nonaka
Manabu
M
Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan. nonaka@nms.ac.jp
Fukumoto
Akira
A
Ogihara
Nozomu
N
Sakanushi
Atsuko
A
Pawankar
Ruby
R
Yagi
Toshiaki
T
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
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D000094632:Thymic Stromal Lymphopoietin