Hydrogen sulfide modulates the release of nitric oxide and VEGF in human keratinocytes

Hydrogen sulfide (H2S) is a novel signaling molecule with both pro- or anti-inflammatory effect. The present study aimed to: (i) characterize the in vitro effects of H2S on human keratinocyte's proliferation and death; (ii) investigate the ability of H2S to modulate VEGF and NO production; (iii) examine the intracellular signaling pathways involved in VEGF and NO modulatory effect. We found that exogenous application of H2S (NaHS and GYY4137 as H2S donors) significantly enhances NO through increase of iNOS, in a manner Akt-dependent. The increment in NO down-regulates ERK1/2 activation thereby resulting in the decrease of VEGF release. We suggest that H2S-releasing agents may be promising therapeutics for chronic inflammatory disorders of the skin, i.e. psoriasis, in which NO increases as well as anti-VEGF treatments have been suggested to be novel effective approaches.