A novel mouse model for Sezary Syndrome using xenotransplantation of Sezary cells into immunodeficient RAG2-/-gamma c-/- mice

作者:van der Fits Leslie*; Rebel Heggert G; Out Luiting Jacoba J; Pouw Stephan M; Smit Fiona; Vermeer Kim G; van Zijl Lisanne; Tensen Cornelis P; Weijer Kees; Vermeer Maarten H
来源:Experimental Dermatology, 2012, 21(9): 706-709.
DOI:10.1111/j.1600-0625.2012.01556.x

摘要

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%26apos;-triphosphate (ATP) and adenosine-5%26apos;-O-(3-thio) triphosphate (ATP?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 a) by dermal microvascular ECs. Production of these chemokines can also be induced by the exposure to the proinflammatory cytokine TNFa. We have now demonstrated that AFC dose-dependently inhibits ATP-, ATP?S- and TNFa-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 ATP?S- or TNFa-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.

  • 出版日期2012-9