Cyclosporin-A inhibits human endothelial cells proliferation through interleukin-6-dependent mechanisms.
Cyclosporine A (CsA) is a widely used immunosuppressant which possesses significant side effects including nephrotoxicity and systemic arterial hypertension. In this work we evaluated the effects of CsA on human umbilical endothelial cell proliferation (HUVEC). Treatment of endothelial cells with CsA inhibited cell proliferation, and was correlated with an increase of interleukin-6 (IL-6) production and IL-6 mRNA expression. Addition of exogenous IL-6 also significantly altered cell proliferation. Furthermore, neutralization of endogenous IL-6 with a specific monoclonal antibody concomitantly with CsA treatment completely restored HUVEC proliferation. These results suggest that CsA-induced inhibition of HUVEC proliferation is mediated through an augmentation of IL-6 synthesis.
Storogenko
M
M
Immunotoxicologie et Cancérogenèse, Faculté de Pharmacie Paris-Sud, Chatenay-Malabry, France.
Pech-Amsellem
M A
MA
Kerdine
S
S
Rousselet
F
F
Pallardy
M
M
D000906:Antibodies / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
D000906:Antibodies; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D012333:RNA, Messenger; D016572:Cyclosporine