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Hydrogen sulfide reduces cell adhesion and relevant inflammatory triggering by preventing ADAM17‐dependent TNF‐α activation
Author(s) -
Perna Alessandra F.,
Sepe Immacolata,
Lanza Diana,
Capasso Rosanna,
Zappavigna Silvia,
Capasso Giovambattista,
Caraglia Michele,
Ingrosso Diego
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24495
Subject(s) - chemistry , cell adhesion molecule , microbiology and biotechnology , cell adhesion , tumor necrosis factor alpha , ectodomain , monocyte , endothelial stem cell , chemokine , nitric oxide , proinflammatory cytokine , inflammation , receptor , biochemistry , biology , cell , immunology , in vitro , organic chemistry
H 2 S is the third endogenous gaseous mediator, after nitric oxide and carbon monoxide, possessing pleiotropic effects, including cytoprotection and anti‐inflammatory action. We analyzed, in an in vitro model entailing monocyte adhesion to an endothelial monolayer, the changes induced by H 2 S on various potential targets, including cytokines, chemokines, and proteases, playing a crucial role in inflammation and cell adhesion. Results show that H 2 S prevents the increase in monocyte adhesion induced by tumor necrosis factor‐α (TNF‐α). Under these conditions, downregulation of monocyte chemoattractant protein‐1 (MCP‐1), chemokine C‐C motif receptor 2, and increase of cluster of differentiation 36 could be detected in monocytes. In endothelial cells, H 2 S treatment reduces the increase in MCP‐1, inter‐cellular adhesion molecule‐1, vascular cell adhesion molecule‐1, and of a disintegrin and metalloproteinase metallopeptidase domain 17 (ADAM17), both at the gene expression and protein levels. Cystathionine γ‐lyase and 3‐mercaptopyruvate sulfurtransferase, the major H 2 S forming enzymes, are downregulated in endothelial cells. In addition, H 2 S significantly reduces activation of ADAM17 by PMA in endothelial cells, with consequent reduction of both ADAM17‐dependent TNF‐α ectodomain shedding and MCP‐1 release. In conclusion, H 2 S is able to prevent endothelial activation by hampering endothelial activation, triggered by TNF‐α. The mechanism of this protective effect is mainly mediated by down‐modulation of ADAM17‐dependent TNF‐converting enzyme (TACE) activity with consequent inhibition of soluble TNF‐α shedding and its relevant MCP‐1 release in the medium. These results are discussed in the light of the potential protective role of H 2 S in pro‐inflammatory and pro‐atherogenic processes, such as chronic renal failure. J. Cell. Biochem. 114: 1536–1548, 2013. © 2013 Wiley Periodicals, Inc.