Hydrogen sulfide inhibits IL-8 expression in human keratinocytes via MAP kinasesignaling

Sulfur is able to penetrate the skin, and a sulfur-rich balneotherapy has been
suggested to be effective in the treatment of psoriasis. Psoriasis is now
considered a genetically programmed, immune-mediated, inflammatory disease, in
which intralesional T lymphocytes trigger keratinocytes to proliferate and
perpetuate the disease process. Interleukin (IL)-17 and IL-22 produced by
Th1/Th17 lymphocytes induce IL-8 secretion by keratinocytes, a key event in the
pathogenesis of the disease. It is now clear that mitogen-activated protein
kinase (MAPK) (extracellular signal-regulated kinases (ERK) 1 and 2) activity is
required for IL-17-induced IL-8 synthesis by keratinocytes, and, in fact, MAPK
activity is increased in lesional psoriatic skin. Here, we demonstrate both in
vitro and in vivo on primary psoriatic lesions that pharmacological inhibitors of
ERKs as well as hydrogen sulfide not only reduce the basal expression and
secretion of IL-8, but also interfere with IL-17- and IL-22-induced IL-8
production. These observations, together with the known anti-inflammatory
activity of H₂S, are relevant to understanding some previously unexplained
biological effects exerted by sulfur therapy.