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

Authors


Terada Department of Otorhinolaryngology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260–0856, Japan (e-mail: terada@med.m.chiba-u.ac.jp).

Abstract

Background

There is increasing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. However, the mechanism involved in the production of eotaxin has yet to be clarified. Most recently, it has been shown that interleukin (IL) -4 induces eotaxin in dermal fibroblasts. A novel cytokine termed IL-13, which binds to the α-chain of the IL-4 receptor, shares many biological activities with IL-4. It is known that fibroblasts 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 induce eotaxin production in human nasal mucosal fibroblasts (HNMFs). Furthermore, we investigated the effect of costimulation of IL-13 and TNFα on eotaxin production.

Methods

HNMFs, isolated from inferior nasal mucosa samples, were stimulated by various kind of cytokines for 1–36 h at 37 °C in 5% CO2. The change in the expression of eotaxin mRNA was then evaluated by reverse transcriptase-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 in HNMFs. Furthermore, IL-13 and TNFα synergistically induced eotaxin expression in HNMFs, while they hardly induced eotaxin expression in endothelial cells, epithelial cells or eosinophils. The synergy was observed when pre-incubation of HNMFs with IL-13 was followed by a stimulation with TNFα, or HNMFs were simultaneously stimulated with IL-13 and TNFα.

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 eotaxin.

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