Wang W, Tam W F, Hughes C C, Rath S, Sen R
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02254, USA.
Immunity. 1997 Feb;6(2):165-74. doi: 10.1016/s1074-7613(00)80423-9.
The possible clinical use of the methyl xanthine derivative, pentoxifylline (PF), for the treatment of T cell-dependent diseases is being noted with increasing interest. In this paper, we studied the molecular consequences of PF treatment during lymphocyte activation. We found that in T cells, anti-CD3-induced c-Rel expression was blocked by PF, whereas the induction of other NF-kappaB family members was not significantly affected. However, induction of NF-AT, which has the same signaling requirements as c-Rel induction, was not inhibited by PF. Among genes that respond to these transcription factors, IL-2 mRNA induction was suppressed by PF, whereas IL-2R(alpha) chain mRNA induction was not affected. These observations implicated c-Rel as an IL-2 promoter factor, for which experimental support was obtained from transient transfection experiments. In contrast with the observation in T cells, c-Rel induction was not blocked by PF in B cells. The greater selectivity of PF, compared with FK506, at both the molecular and cellular levels may prove advantageous in manipulating T cell responses in vivo.
甲基黄嘌呤衍生物己酮可可碱（PF）在治疗T细胞依赖性疾病方面的潜在临床应用正受到越来越多的关注。在本文中，我们研究了PF处理对淋巴细胞激活过程的分子影响。我们发现，在T细胞中，抗CD3诱导的c-Rel表达被PF阻断，而其他NF-κB家族成员的诱导未受到显著影响。然而，与c-Rel诱导具有相同信号需求的NF-AT的诱导并未被PF抑制。在对这些转录因子有反应的基因中，PF抑制了IL-2 mRNA的诱导，而IL-2R（α）链mRNA的诱导未受影响。这些观察结果表明c-Rel是一种IL-2启动子因子，瞬时转染实验为其提供了实验支持。与在T细胞中的观察结果相反，PF在B细胞中并未阻断c-Rel的诱导。与FK506相比，PF在分子和细胞水平上具有更高的选择性，这可能在体内调节T细胞反应方面具有优势。
