| 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 | Ilaria Dal Pra, Anna Chiarini, Raffaella Pacchiana, Giuseppe Zumiani, Mauro Zanoni, Ubaldo Armato
(Affiliation: Histology and Embryology Unit, Department of Biomedical and Surgical Sciences, University of Verona Medical School, Verona I-37134, Italy.)
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| Journal | International journal of molecular medicine
(Int J Mol Med)
Vol. 19
Issue 3
Pg. 373-9
(Mar 2007)
ISSN: 1107-3756 Greece |
| PMID | 17273783
(Publication Type: Journal Article)
|
| Chemical References |
- Interleukin-8
- Tumor Necrosis Factor-alpha
- Water
|
| Topics |
- Balneology
- Cells, Cultured
- Down-Regulation
(drug effects)
- Humans
- Interleukin-8
(biosynthesis, secretion)
- Italy
- Keratinocytes
(cytology, drug effects, pathology)
- Psoriasis
(pathology)
- Tumor Necrosis Factor-alpha
(metabolism, secretion)
- Water
(chemistry, pharmacology)
|