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.

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.