Comano's (Trentino) thermal water interferes with interleukin-6 production and secretion and with cytokeratin-16 expression by cultured human psoriatic keratinocytes: Further potential mechanisms of its anti-psoriatic action

Abstract

Abstract. 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 keratinocytes 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.

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

“…Here, we will show that the addition of CW (in total or partial stead of DW) to the growth medium remarkably hinders the hyper-expression of TNF-· and the heightened production and release of IL-8 on the part of the psoriatic keratinocytes. Therefore, our previous (49,50) and present findings are consistent with CW being endowed with a complex phenotype-and cytokine/chemokine-regulating potential that translates into valuable anti-psoriatic therapeutic benefits.…”

“…In conclusion, our previous (49,50) and present observations support the view that CW balneotherapy may elicit its beneficial effects by interfering with an improper local production and secretion of several chemokines and cytokines, including TNF-·, IL-8, IL-6, and various VEGF-A isoforms, and by attenuating some facets, such as CK-16 expression, of the psoriatic phenotype, which altogether locally underlie the epidermal hyperplasia and dermal neoangiogenesis, inflammation, and leukocyte infiltration phenomena proper of psoriatic illness.…”

“…Hence, it seems conceivable to ascribe the previously observed interfering effects of CW on IL-6 production and secretion (50) and the presently reported hindering of IL-8 synthesis and release by CW to an up-stream inhibition of TNF-· expression by the same CW components.…”

“…In previous studies (49,50), we showed that exposure to CW interferes with IL-6, VEGF-A isoform, and CK-16 expression by human psoriatic keratinocytes. To further clarify the mechanisms involved in the therapeutic effectiveness of CW balneotherapy in psoriasis, in this study we investigated CW's effects on TNF-· and IL-8 production and secretion by epidermal keratinocytes isolated from lesional skin biopsies and kept in confluent cultures.…”

Balneotherapy for atopic dermatitis in children at Comano spa in Trentino, Italy

“…Despite the fact that balneotherapy has been used for a long time with apparent good clinical results, the mechanism of action is unknown. Recent studies have shown that Comano water can effectively reduce the production of factors relevant to the pathogenesis of psoriasis (15)(16)(17) and that balneotherapy can represent an interesting adjuvant or alternative therapy for psoriasis patients willing to discontinue pharmacologic therapy (18).…”