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

Authors: Merighi S (1) , Gessi S , Varani K , Fazzi D , Borea PA
(1) Department of Clinical and Experimental Medicine, Pharmacology Section and Interdisciplinary Center for the Study of Inflammation, University of Ferrara
Source: Pharmacol Res. 2012 Nov;66(5):428-36
DOI: 10.1016/j.phrs.2012.07.002 Publication date: 2012 Nov E-Publication date: July 27, 2012 Availability: abstract Copyright: © 2012 Elsevier Ltd. All rights reserved.
Language: English Countries: Not specified Location: Not specified Correspondence address: Pier Andrea Borea : Tel.: +39 0532 455202; fax: +39 0532 455205. email : bpa@unife.it


Article 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.

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