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Mol Biol Rep (2010) 37:27032709 DOI 10.1007/s11033-009-9804-z
The inuence of ADAR1s regulation on lymphocyte cell function during rejection
Lei Cai Yan Li Feng Liu Wei Zhang Binliang Huo Wei Zheng Rui Ding Jiyuan Guo Qingchuan Zhao Kefeng Dou
Received: 26 May 2009 / Accepted: 2 September 2009 / Published online: 15 September 2009 Springer Science+Business Media B.V. 2009
Abstract The RNA editing adenosine deaminase gene (ADAR1) expression is wide-spread in lymphocytes. We explore the mechanism of ADAR1 regulation on the function of T primary lymphocytes when rejection occurs by knock-down the expression of ADAR1 in mouse T primary lymphocytes in mixed lymphocyte cultures. The changes of cell proliferation, the expression of ADAR1 and the cell cycle related genes cyclin D1 and A1, cell cycle and apoptosis analysis and mouse gene expression proles was evaluated. We found that treatment with ADAR1-specic siRNA inhibited allogenic antigen stimulated T cell proliferation, arrested T cell cycle at G0/G1 phases and
promoted T cell apoptosis, which was associated with down-regulation of some related key genes transcription. These ndings suggest that ADAR1 is essential for the maintenance of function of T lymphocytes during acute rejection. The mechanism underlying ADAR1s action might include editing of a currently unknown substrate and interacting with other proteins.
Keywords ADAR1 Mixed lymphocyte culture
T primary lymphocyte Acute rejection RNAi
Introduction
Despite advances in immunosuppression, allograft loss due to acute rejection remains a formidable clinical problem [13]. Although the RNA editing adenosine deaminase gene ADAR1 alone is not sufcient to mediate acute allograft rejection, more and more attention has been paid to the role of this molecule during acute rejection.
ADAR1 is a typical double-stranded RNA (dsRNA) binding protein (DRBP) that modies dsRNA and predsRNA by adenosine deamination. In mammals, two homologous genes encoding ADAR1 have been identied, each of which is endowed with domain or dsRNA binding on pre-RNA and preferably convert adenosines in dsRNA. Recent studies have shown that ADAR1 may interfere with other DRBPs by sequestering the cellular dsRNA components, such as nuclear factor 90 (NF90) family proteins [4].
ADAR1 is ubiquitously expressed in immune organs [4]. Thus, the function of ADAR1 has been implicated in host defense mechanisms [57]. ADAR1 is upregulated in response to viral and microbial infection and to local, [8]...