Comano's (Trentino) thermal water interferes with the expression and secretion of vascular endothelial growth factor-A protein isoforms by cultured human psoriatic keratinocytes: a potential mechanism of its anti-psoriatic action.
Thermal balneotherapy with Comano spa's water (CW; Trentino, Italy) is used for psoriasis and other skin disorders but the mechanism(s) of action of this hypotonic water are unknown. Since skin psoriatic manifestations are thought to be angiogenesis-dependent, we assessed CW's effects on the expression and release of VEGF-A protein isoforms by cultured human lesional keratinocytes isolated from skin biopsies performed in 9 patients. Confluent, psoriatic keratinocytes were exposed for 11 days to DMEM, whose chemicals had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells). As detected by Western immunoblotting (WB), incubation in CW-DMEM elicited, with respect to DW-DMEM, an increase in intracellular and/or cell-bound L-VEGF-A189 and L-VEGF-A165 48 kDa protein isoforms with no concurrent change in L-VEGF-A121 and L-VEGF-A165 45 kDa proteins. Moreover, WB analysis of the secreted VEGF-A (sVEGF-A) proteins showed that the 20 and 15 kDa bands corresponding to different VEGF-A isoforms were directly and remarkably reduced in keratinocyte-conditioned CW-DMEM vs. DW-DMEM. Thus, CW interferes with VEGF-A isoform expression and secretion by the psoriatic keratinocytes. These effects would reduce all VEGF-A-mediated angiogenic, vessel permeabilising, and chemotactic effects, thereby at least in part explaining the beneficial actions of CW balneotherapy on the clinical manifestations of psoriasis.
Chiarini
Anna
A
Histology and Embryology Unit, Department of Biomedical and Surgical Sciences, University of Verona Medical School, I-37134 Verona, Italy.
Dal Pra
Ilaria
I
Pacchiana
Raffaella
R
Menapace
Lia
L
Zumiani
Giuseppe
G
Zanoni
Mauro
M
Armato
Ubaldo
U
D002478:Cells, Cultured; D006801:Humans; D007038:Hypotonic Solutions / Q000627:therapeutic use; D007558:Italy; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008900:Mineral Waters / Q000008:administration & dosage* / Q000627:therapeutic use; D020033:Protein Isoforms / Q000096:biosynthesis / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
D007038:Hypotonic Solutions; D008900:Mineral Waters; D020033:Protein Isoforms; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A