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.
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.
Chiarini
Anna
A
Histology and Embryology Unit, Department of Biomedical and Surgical Sciences, University of Verona Medical School, Verona I-37134, Italy.
Dal Pra
Ilaria
I
Pacchiana
Raffaella
R
Zumiani
Giuseppe
G
Zanoni
Mauro
M
Armato
Ubaldo
U
D002478:Cells, Cultured; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism*; D007558:Italy; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D007633:Keratins / Q000378:metabolism*; D008900:Mineral Waters / Q000008:administration & dosage* / Q000627:therapeutic use; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D015850:Interleukin-6; D008900:Mineral Waters; D007633:Keratins