Treponema denticola immunoinhibitory protein induces irreversible G1 arrest in activated human lymphocytes.
Treponema denticola immunoinhibitory protein induces irreversible G1 arrest in activated human lymphocytes.
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密螺旋体免疫抑制蛋白可诱导活化的人淋巴细胞不可逆的 G1 期停滞。
DOI：
10.1111/j.0902-0055.2004.00129.x
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Shenker,BJ
中科院分区：
文献类型：
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作者：
Lee,W;Pankoski,L;Zekavat,A;Shenker,BJ
口腔螺旋体可能导致包括牙周病和根周疾病在内的许多疾病的发病机制;然而，这些生物体引起疾病的机制尚不清楚。我们以前已经表明，提取物的口腔螺旋体，齿垢密螺旋体，含有免疫抑制蛋白（Sip），损害人类淋巴细胞增殖。本研究的目的是确定Sip改变淋巴细胞增殖反应的机制。在存在或不存在Sip的情况下通过PHA活化人T细胞，并通过流式细胞术评估细胞周期进展。细胞周期分布基于DNA、RNA和蛋白质含量以及活化标志物CD 69和IL-2 R的表达。在PHA活化后72小时，发现细胞处于细胞周期的G 0、G1、S和G2/M期。与此相反，Sip预处理导致S期和G2/M期细胞显著减少，同时G1期细胞增加。Sip没有改变早期活化标志物CD 69和CD 25 R的表达。为了确定G1阻滞是否导致检查点激活和细胞死亡，我们还监测了Sip处理的细胞的凋亡。事实上，用Sip处理导致96小时后DNA断裂和半胱天冬酶活化。 我们的研究结果表明，Sip诱导人T细胞的G1期阻滞，而且这种阻滞是不可逆的，最终导致凋亡级联反应的激活。我们认为，如果细胞周期停滞发生在体内，它可能会导致局部和/或全身免疫抑制，从而增强螺旋体和/或其他机会微生物的致病性。
Oral spirochetes may contribute to the pathogenesis of a number of disorders including periodontal and periradicular diseases; however, the mechanism (s) by which these organisms act to cause disease is unknown. We have previously shown that extracts of the oral spirochete,Treponema denticola,contain an immunosuppressive protein (Sip) which impairs human lymphocyte proliferation. The objective of this study was to determine the mechanism by which Sip alters the proliferative response of lymphocytes. Human T‐cells were activated by PHA in the presence or absence of Sip and cell cycle progression was assessed by flow cytometry. Cell cycle distribution was based upon DNA, RNA and protein content as well as expression of the activation markers; CD69 and IL‐2R. Seventy‐two hours following activation with PHA, cells were found in the G0, G1, S and G2/M phases of the cell cycle. In contrast, pretreatment with Sip resulted in a significant reduction of cells in the S and G2/M phases and a concomitant increase in the G1phase. Sip did not alter the expression of the early activation markers CD69 and CD25R. To determine if G1arrest resulted in activation of the checkpoint and cell death, we also monitored Sip‐treated cells for apoptosis. Indeed, treatment with Sip resulted in both DNA fragmentation and caspase activation after 96 h. Our results indicate that Sip induces G1arrest in human T‐cells and, furthermore, that the arrest is irreversible, culminating in activation of the apoptotic cascade. We propose that if cell cycle arrest occursin vivo, it may result in local and/or systemic immunosuppression and thereby enhance the pathogenicity of spirochetes and/or that of other opportunistic organisms.