RANTES PRODUCTION BY CYTOKINE-STIMULATED NASAL FIBROBLASTS - ITS INHIBITION BY GLUCOCORTICOIDS

Nasal fibroblasts play an important role in both nasal polyposis and n asal allergic diseases and they are known to release a number of proin flammatory cytokines, including GM-CSF, IL-8 and IL-6. The aim of this present work was to investigate whether cytokine-stimulated nasal fib roblasts release biologically active RANTES as well as to study the ef fect of corticosteroids on the ability of nasal fibroblasts to produce the cytokine. Measurements of RANTES by ELISA demonstrated that RANTE S is constitutively secreted spontaneously (21+/-4 vs. 19+/-6 ng/ml, r espectively p>0.05). Stimulation of these cells with either TNF-alpha, IL-1 beta or IFN-gamma induce further release of RANTES in a dose-dep endent manner with TNF-alpha being the most potent stimulus. RANTES mR NA expression in nasal fibroblasts correlated with the amount of prote in released in the culture supernatant upon cytokine stimulation. More over, chemotaxis studies demonstrated that the nasal-derived RANTES wa s biologically active on eosinophils. Betamethasone and hydrocortisone were found to downregulate RANTES mRNA expression in TNF-alpha-stimul ated fibroblasts. These observations suggest that RANTES released by n asal fibroblasts may regulate eosinophil recruitment in nasal disease while glucocorticoids may inhibit the influx of these cells by suppres sing the production of RANTES.