Premium
N ‐acetyl‐ S ‐farnesyl‐ l ‐cysteine suppresses chemokine production by human dermal microvascular endothelial cells
Author(s) -
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.
Publication year - 2012
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2012.01562.x
Subject(s) - chemokine , proinflammatory cytokine , chemistry , microbiology and biotechnology , cytokine , inflammation , pharmacology , biology , biochemistry , receptor , immunology
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 ( EC s) 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 ( ATP γ S ), an ATP analogue that is resistant to hydrolysis, increase secretion of the chemokines CXCL 8 (interleukin‐8), CCL 2 (monocyte chemotactic protein‐1) and CXCL 1 (growth‐regulated oncogene α) by dermal microvascular EC s. Production of these chemokines can also be induced by the exposure to the proinflammatory cytokine TNF α. We have now demonstrated that AFC dose‐dependently inhibits ATP ‐, ATP γ S ‐ and TNF α‐induced production of CXCL 1, CXCL 8 and CCL 2 by a human dermal microvascular EC line ( HMEC ‐1) in vitro under conditions that do not affect cell viability. Inhibition of ATP γ S ‐ or TNF α‐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 EC s.