Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 5, Issue 5, Pages 1042-1049Publisher
WILEY
DOI: 10.1111/j.1600-6143.2005.00807.x
Keywords
allograft; vasculopathy; IL-1; IL-10; IL-6; IL-1ra; darusentan; endothelin; gene expression; heart; immunoassay; interleukin; liver; lung; LU135252; mRNA; protein; transplantation; TNF-alpha
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This study investigated whether allograft rejection is associated with local inflammatory activation in host organs and whether endothelin ETA receptor signaling is involved. Expression of IL-1 beta, IL-1ra, IL-6, IL-10 and TNF-alpha was investigated in host liver, lung and native heart in a rat model of chronic rejection 8 weeks after heterotopic cardiac transplantation in the absence of immunosuppression. In the presence of rejection, circulating levels of cytokines increased, while tissue level activation was dependent on the organ involved. Similarly, tissue-specific regulatory patterns were observed regarding transcriptional activation. Although chronic ETA receptor blockade did not reduce transplant vasculopathy or tissue protein expression, treatment had pronounced effects on plasma levels and transcriptional regulation of chemokines. These data provide evidence for distinct pro-inflammatory local activation in host organs during chronic rejection and suggest a role for ETA receptors contributing to regulation of cytokine plasma levels and transcriptional activity.
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