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The malononitrilamide FK778 inhibits activation of NF-kappaB in human dendritic cells.

Abstract：

:FK778, a derivative of the active leflunomide-metabolite, A77 1726, has been shown to be a powerful immunosuppressant in several transplantation models, particularly efficient in prevention of chronic allograft rejection. However, the cellular and molecular mechanisms underlying these effects of FK778 have not been investigated yet in detail. Because dendritic cells (DCs) are a crucial cell type in initiation of immune responses including chronic allograft rejection, we investigated whether FK778 affects this peculiar cell population. NF-kappaB is the essential transcription factor involved in DC activation and function. We found that lipopolysaccharide (LPS)-induced activation of NF-kappaB, as assessed using electromobility shift assay, is markedly inhibited by FK778 in human monocyte-derived DCs. Hence, FK778 could exert its immunosuppressive effects via inhibition of activation and thus function of the central antigen-presenting cell, ie, DC.

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Zeyda M,Stuhlmeier KM,Kirsch B,Watschinger B,Hörl WH,Stulnig TM,Säemann MD

doi

10.1016/j.transproceed.2005.03.079

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

1968-9

issue

4

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(05)00318-0

journal_volume

37

pub_type

杂志文章

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