Comano's (Trentino) thermal water interferes with tumour necrosis factor-α expression and interleukin-8 production and secretion by cultured human psoriatic keratinocytes: Yet other mechanisms of its anti-psoriatic action

Thermal balneotherapy with Comano's spa water (CW; Trentino, Italy) is beneficial for psoriasis and other skin disorders but its operative mechanisms are largely unknown. Previously, we showed that CW interferes with the production and secretion of IL-6 and various VEGF-A isoforms and with CK-16 expression by cultured human psoriatic keratinocytes. In this study, confluent cultures of epidermal keratinocytes isolated from the lesional areas of 9 psoriatic patients were exposed for 11-13 days to DMEM, whose chemicals had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells), in order to assess the expression and secretion of TNF-α and IL-8 by such cells. The results gained by means of immunocytochemistry, Western immunoblotting (WB), and ELISA assays showed that CW exposure significantly down-regulated the intracellular levels of TNF-α, a key inducer of IL-8, IL-6, and other chemokines. However, no assayable TNF-α secretion occurred in keratinocyte-conditioned DW- and CW-DMEM samples. Moreover, the intracellular levels and secretion rates of IL-8 were also markedly reduced in the protein extracts and conditioned media of CW-DMEM-incubated keratinocytes. Notably, the most effective inhibition of IL-8 secretion was elicited by a 25% CW fraction in the DMEM. Altogether, our findings indicate that by attenuating at lesional skin sites the deregulated production and secretion of a cascade of several cytokines and chemokines (e.g. TNF- α, IL-8, IL-6, and various VEGF-A isoforms), and by offsetting the keratinocytes' abnormal differentiation program entailing CK-16 expression, CW balneotherapy may beneficially influence the clinical manifestations of psoriasis.