Upregulation of endothelin converting enzyme-1 in host liver during chronic cardiac allograft rejection.
Endothelin regulates cytokine expression in vitro and in vivo. This study investigated the effects of chronic allograft rejection on hepatic endothelin-converting enzyme-1 (ECE-1) gene expression and endothelin-1 (ET-1) plasma clearance. Using the Lewis-F344 minor histocompatibility mismatch model of heterotopic cardiac transplantation, hepatic ECE-1 gene expression was measured by real-time polymerase chain reaction and host plasma clearance of ET-1 was measured 8 weeks after transplantation in the absence of immunosuppression. In animals undergoing allograft rejection, hepatic ECE-1 gene expression increased 2-fold (P < 0.05), whereas no effect of rejection on ET-1 clearance from plasma was observed. In summary, upregulation of ECE-1 gene expression occurs in the liver of the host during chronic allograft rejection. Because the liver represents both a key organ for cytokine production and for endothelin metabolism, increased hepatic ECE-1-mediated ET-1 synthesis may contribute to host responses and cytokine production during allograft rejection.
Lattmann
Thomas
T
Medical Policlinic, Department of Medicine, University Hospital, Rämistrasse 100, CH-8091 Zürich, Switzerland.
Ortmann
Jana
J
Horber
Sibylle
S
Shaw
Sidney G
SG
Hein
Marc
M
Barton
Matthias
M
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D002908:Chronic Disease; D019332:Endothelin-1 / Q000493:pharmacokinetics; D000072396:Endothelin-Converting Enzymes; D015971:Gene Expression Regulation, Enzymologic; D006084:Graft Rejection; D016027:Heart Transplantation; D008099:Liver / Q000201:enzymology* / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013997:Time Factors; D014184:Transplantation, Homologous; D015854:Up-Regulation
D019332:Endothelin-1; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes