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Expression of C–C chemokine TARC in human nasal mucosa and its regulation by cytokines

Authors


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

Abstract

Background Although interleukin (IL)-4 and IL-5 have been demonstrated to play a critical role in the pathophysiology of allergic diseases such as allergic rhinitis, the mechanism that causes the predominance of Th2 lymphocytes has yet to be clarified. Thymus and activation-regulated chemokine (TARC) has been known to facilitate the recruitment, activation and development of Th2 polarized cells, leading investigators to suggest a role for TARC in the development of Th2 responses.

Objective To gain a better understanding of the role of TARC in the pathogenesis of allergic rhinitis we investigated the cellular sources of this chemokine in nasal mucosa. In addition, the effect of cytokines on TARC production has been investigated.

Methods The expression of TARC in human nasal mucosa was assessed by immunohistochemistry. To study the effect of cytokines on TARC production, epithelial cells, endothelial cells and fibroblasts, isolated from inferior nasal mucosa samples, were stimulated by a variety of cytokines including IL-4, IL-13, tumour necrosis factor (TNF)-α and interferon (IFN)-γ.

Results Epithelial cells in nasal mucosa in subjects with allergic rhinitis expressed higher signal level than those in non-allergy patients. Combined stimulation with IL-4 and TNF-α, as well as IL-13 and TNF-α, synergistically induced TARC expression in epithelial cells. Furthermore, the amount of TARC induced by these cytokines was higher in epithelial cells obtained from patients with allergic rhinitis than in those from non-allergic patients.

Conclusion These results demonstrate a crucial role of nasal epithelial cells in the expression of TARC, and that Th2 cytokine IL-4 and IL-13 may promote Th2 responses by inducing TARC production from epithelial cells.

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