title: Comano's (Trentino) thermal water interferes with tumour necrosis factor-alpha expression and interleukin-8 production and secretion by cultured human psoriatic keratinocytes: yet other mechanisms of its anti-psoriatic action.
abstract: 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-alpha 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-alpha, a key inducer of IL-8, IL-6, and other chemokines. However, no assayable TNF-alpha 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- alpha, 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.
authors.affiliation: Histology and Embryology Unit, Department of Biomedical and Surgical Sciences, University of Verona Medical School, Verona I-37134, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dal Pra
authors.forename: Anna
authors.initials: A
authors.lastname: Chiarini
authors.forename: Raffaella
authors.initials: R
authors.lastname: Pacchiana
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zumiani
authors.forename: Mauro
authors.initials: M
authors.lastname: Zanoni
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Armato
mesh_terms: D001452:Balneology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism*; D007558:Italy; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D011565:Psoriasis / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014867:Water / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D014867:Water