RANTES Production by Cytokine–Stimulated Nasal Fibroblasts: Its Inhibition by Glucocorticoids

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Abstract
Nasal fibroblasts play an important role in both nasal polyposis and nasal allergic diseases and they are known to release a number of proinflammatory cytokines, including GM–CSF, IL–8 and IL–6. The aim of this present work was to investigate whether cytokine–stimulated nasal fibroblasts release biologically active RANTES as well as to study the effect of corticosteroids on the ability of nasal fibroblasts to produce the cytokine. Measurements of RANTES by ELISA demonstrated that RANTES is constitutively secreted spontaneously (21±4 vs. 19±6 ng/ml, respectively p>0.05). Stimulation of these cells with either TNF–α, IL–1β or IFN–γ induce further release of RANTES in a dose–dependent manner with TNF–α being the most potent stimulus. RANTES mRNA expression in nasal fibroblasts correlated with the amount of protein released in the culture supernatant upon cytokine stimulation. Moreover, chemotaxis studies demonstrated that the nasal–derived RANTES was biologically active on eosinophils. Betamethasone and hydrocortisone were found to downregulate RANTES mRNA expression in TNF–α–stimulated fibroblasts. These observations suggest that RANTES released by nasal fibroblasts may regulate eosinophil recruitment in nasal disease while glucocorticoids may inhibit the influx of these cells by suppressing the production of RANTES.