Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis
Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis
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DOI：
10.1111/j.1462-5822.2007.00931.x
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发表时间：
2007-08-01
影响因子：
3.4
通讯作者：
Lamont, Richard J.
中科院分区：
文献类型：
--
作者：
Mao, Song;Park, Yoonsuk;Lamont, Richard J.
牙龈卟啉单胞菌通过阻断caspase-3的激活抑制化学诱导的牙龈上皮细胞凋亡。牙龈卟啉单胞菌的抗细胞凋亡表型在菌株间是保守的，并且不依赖于菌毛的存在，因为菌毛缺陷突变体和天然存在的非菌毛菌株能够阻碍细胞凋亡。为了剖析由牙龈卟啉单胞菌调节的存活途径，研究了凋亡死亡途径的许多组分的蛋白质和基因表达。牙龈卟啉单胞菌感染上皮细胞导致JAK 1和Stat 3磷酸化。实时定量逆转录聚合酶链反应显示，在牙龈卟啉单胞菌感染的细胞中，活化的Stat 3的靶蛋白Survivin和Stat 3本身的表达升高。JAK 1的siRNA敲除与Akt的敲除组合，消除了牙龈卟啉单胞菌阻断细胞凋亡的能力。与此相反，cIAP-1和cIAP-2在蛋白质或mRNA水平上没有被牙龈卟啉单胞菌差异调节。因此，牙龈卟啉单胞菌可以阻断牙龈上皮细胞中的凋亡途径的一种机制是通过操纵控制内在线粒体细胞死亡途径的JAK/Stat途径。促存活表型的诱导可以防止程序性宿主细胞死亡并帮助牙龈卟啉单胞菌在牙龈上皮细胞内存活。
Porphyromonas gingivalis can inhibit chemically induced apoptosis in primary cultures of gingival epithelial cells through blocking activation of the effector caspase-3. The anti-apoptotic phenotype of P. gingivalis is conserved across strains and does not depend on the presence of fimbriae, as fimbriae-deficient mutants and a naturally occurring non-fimbriated strain were able to impede apoptosis. To dissect the survival pathways modulated by P. gingivalis, protein and gene expression of a number of components of apoptotic death pathways were investigated. P. gingivalis infection of epithelial cells resulted in the phosphorylation of JAK1 and Stat3. Quantitative real-time reverse transcription polymerase chain reaction showed that expression of Survivin and Stat3 itself, targets of activated Stat3, were elevated in P. gingivalis-infected cells. siRNA knockdown of JAK1, in combination with knockdown of Akt, abrogated the ability of P. gingivalis to block apoptosis. In contrast, cIAP-1 and cIAP-2 were not differentially regulated at either the protein or mRNA levels by P. gingivalis. One mechanism by which P. gingivalis can block apoptotic pathways in gingival epithelial cells therefore is through manipulation of the JAK/Stat pathway that controls the intrinsic mitochondrial cell death pathways. Induction of a pro-survival phenotype may prevent programmed host cell death and aid survival of P. gingivalis within gingival epithelial cells.