Frazer-Abel Ashley A, McCue Jesica M, Lazis Sabine, Portas Mary, Lambert Cherie, Freed Brian M
Division of Allergy and Clinical Immunology, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA.
Mol Immunol. 2007 Jan;44(4):488-93. doi: 10.1016/j.molimm.2006.02.013. Epub 2006 Apr 11.
Cigarette smoking causes profound suppression of pulmonary T cell responses, which is associated with increased susceptibility to respiratory tract infections and decreased tumor surveillance. We previously demonstrated that the phenolic compounds in cigarette tar inhibit blastogenesis and interfere with human T cell cycle progression. To identify the mechanism by which cell cycle arrest occurs, we examined the effects of these compounds on cyclin-dependent kinases (Cdk) that control the G0/G1 transition. We found that hydroquinone inhibited induction of Cdk4 and Cdk6 kinase activities by >80%, while catechol and phenol were markedly less potent. HQ did not affect mitogenic induction of the Cdk6 protein, but inhibited expression of cyclin D3 by >90% resulting in a dramatic reduction in proper Cdk6/Cyclin D3 complex formation.
吸烟会导致肺部T细胞反应受到严重抑制，这与呼吸道感染易感性增加和肿瘤监测能力下降有关。我们之前证明，香烟焦油中的酚类化合物会抑制细胞增殖并干扰人类T细胞周期进程。为了确定细胞周期停滞发生的机制，我们研究了这些化合物对控制G0/G1期转换的细胞周期蛋白依赖性激酶（Cdk）的影响。我们发现，对苯二酚抑制Cdk4和Cdk6激酶活性的诱导超过80%，而邻苯二酚和苯酚的作用明显较弱。对苯二酚不影响Cdk6蛋白的促有丝分裂诱导，但抑制细胞周期蛋白D3的表达超过90%，导致Cdk6/细胞周期蛋白D3复合物的正常形成显著减少。
