Thermal balneotherapy with Comano's spa water (CW; Trentino, Italy) is used for psoriasis and other skin disorders but its mechanisms of action are mostly unknown. Previously, we showed that CW can interfere with the expression and secretion of various VEGF-A isoforms by cultured human psoriatic epidermal keratinocytes. In this study, confluent cultures of IL-6-hypersecreting keratino-cytes isolated from 6 psoriatic patients were exposed for 11-15 days to DMEM, the chemicals of which had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells). As detected by means of immunocytochemistry, Western immunoblotting, and ELISA assays, the intracellular levels and secretion rates of IL-6 were drastically curtailed in the CW-DMEM-incubated keratinocytes and in their cell-conditioned media. A nearly maximal inhibition of IL-6 release had already been induced by a CW fraction in the DMEM as low as 25%. CW exposure also promptly, intensely, and persistently down-regulated the expression of cytokeratin-16 (CK-16), a marker associated with keratinocyte psoriatic phenotype. Hence, CW balneotherapy may beneficially affect the clinical manifestations of psoriasis via an attenuation of the local deregulation of several cytokines/chemokines, including IL-6 and VEGF-A isoforms, and of a concurrent, abnormal cell differentiation program entailing the expression, amongst other proteins, of CK-16.

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