title: Hydrogen sulfide modulates the release of nitric oxide and VEGF in human keratinocytes.
abstract: Hydrogen sulfide (H(2)S) is a novel signaling molecule with both pro- or anti-inflammatory effect. The present study aimed to: (i) characterize the in vitro effects of H(2)S on human keratinocyte's proliferation and death; (ii) investigate the ability of H(2)S 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 H(2)S (NaHS and GYY4137 as H(2)S 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 H(2)S-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.
authors: Department of Clinical and Experimental Medicine, Pharmacology Section and Interdisciplinary Center for the Study of Inflammation, University of Ferrara, Via Fossato di Mortara, 17/19, 44100 Ferrara, Italy.
authors: Stefania
authors: S
authors: Merighi
authors: Stefania
authors: S
authors: Gessi
authors: Katia
authors: K
authors: Varani
authors: Debora
authors: D
authors: Fazzi
authors: Pier Andrea
authors: PA
authors: Borea
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C529376:GYY 4137; D009025:Morpholines; D009946:Organothiophosphorus Compounds; D013440:Sulfides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C025451:sodium bisulfide; D006862:Hydrogen Sulfide