Interleukin-13 and tumour necrosis factor-alpha synergistically induce eotaxin production in human nasal fibroblasts

Background There is increasing evidence that eotaxin is a key mediator in t he development of tissue eosinophilia. However, the mechanism involved in t he production of eotaxin has yet to be clarified, Most recently, it has bee n shown that interleukin (IL) -4 induces eotaxin in dermal fibroblasts. A n ovel cytokine termed IL-13, which binds to the alpha-chain of the IL-4 rece ptor, shares many biological activities with IL-4. It is known that fibrobl asts express the IL-4 receptor and produce collagen type I upon stimulation with IL-4. Objective We investigated whether IL-13, as well as IL-4, are able to induc e eotaxin production in human nasal mucosal fibroblasts (HNMFs). Furthermor e, we investigated the effect of costimulation of IL-13 and TNF alpha on eo taxin production. Methods HNMFs, isolated from inferior nasal mucosa samples, were stimulated by various kind of cytokines for 1-36 h at 37 degrees C in 5% CO2. The cha nge in the expression of eotaxin mRNA was then evaluated by reverse transcr iptase-polymerase chain reaction and the Southern blot analysis. The amount of eotaxin in the culture media was measured by ELISA. Results IL-13 as well as IL-4 dose-dependently induced eotaxin expression i n HNMFs. Furthermore, IL-13 and TNF alpha synergistically induced eotaxin e xpression in HNMFs, while they hardly induced eotaxin expression in endothe lial cells, epithelial cells or eosinophils, The synergy was observed when pre-incubation of HNMFs with IL-13 was followed by a stimulation with TNF a lpha, or HNMFs were simultaneously stimulated with IL-13 and TNF alpha. Conclusion These results strongly indicate that IL-13, as well as IL-4, may be important in eotaxin-mediated eosinophilic inflammation in nasal mucosa . In addition, in nasal mucosa, fibroblasts are the major cell source for e otaxin.