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- Title
N-acetyl- S-farnesyl- l-cysteine suppresses chemokine production by human dermal microvascular endothelial cells.
- Authors
Adhami, Katayun; Lee, Jason; Levin, Laura; Moquete, Rachel; Stohl, Lori L.; Ding, Wanhong; Wong, Jason; Schierl, Michael; Zhou, Xi K.; Gordon, Joel S.; Perez, Eduardo; Stock, Maxwell B.; Granstein, Richard D.
- Abstract
Isoprenylcysteine ( IPC) molecules modulate G-protein-coupled receptor signalling. The archetype of this class is N-acetyl- S-farnesyl- l-cysteine ( AFC). Topical application of AFC locally inhibits skin inflammation and elicitation of contact hypersensitivity in vivo. However, the mechanism of these anti-inflammatory effects is not well understood. Dermal microvascular endothelial cells ( ECs) are involved in inflammation, in part, by secreting cytokines that recruit inflammatory cells. We have previously shown that the sympathetic nerve cotransmitter adenosine-5′-triphosphate ( ATP) and adenosine-5′- O-(3-thio) triphosphate ( ATPγ S), an ATP analogue that is resistant to hydrolysis, increase secretion of the chemokines CXCL8 (interleukin-8), CCL2 (monocyte chemotactic protein-1) and CXCL1 (growth-regulated oncogene α) by dermal microvascular ECs. Production of these chemokines can also be induced by the exposure to the proinflammatory cytokine TNFα. We have now demonstrated that AFC dose-dependently inhibits ATP-, ATPγ S- and TNFα-induced production of CXCL1, CXCL8 and CCL2 by a human dermal microvascular EC line ( HMEC-1) in vitro under conditions that do not affect cell viability. Inhibition of ATPγ S- or TNFα-stimulated release of these chemokines was associated with reduced mRNA levels. N-acetyl- S-geranyl- l-cysteine, an IPC analogue that is inactive in inhibiting G-protein-coupled signalling, had greatly reduced ability to suppress stimulated chemokine production. AFC may exert its anti-inflammatory effects through the inhibition of chemokine production by stimulated ECs.
- Subjects
ENDOTHELIAL cells; CHEMOKINES; MICROCIRCULATION disorders; SKIN inflammation; INFLAMMATORY mediators; CYTOKINE receptors
- Publication
Experimental Dermatology, 2012, Vol 21, Issue 9, p700
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/j.1600-0625.2012.01562.x