Synergistic induction of thymic stromal lymphopoietin by tumor necrosis factor alpha and Th2 cytokine in nasal polyp fibroblasts

Nonaka, Manabu; Fukumoto, Akira; Ogihara, Nozomu; Sakanushi, Atsuko; Pawankar, Ruby; Yagi, Toshiaki
January 2010
American Journal of Rhinology & Allergy;Jan2010, Vol. 24 Issue 1, p14
Academic Journal
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. Conclusion: 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.


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