B7-H1 and B7-DC receptors of oral squamous carcinoma cells are upregulated by Porphyromonas gingivalis

B7-H1 and B7-DC receptors of oral squamous carcinoma cells are upregulated by Porphyromonas gingivalis
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DOI:
10.1016/j.imbio.2011.05.005
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发表时间:
2011-12-01
期刊:
影响因子:
2.8
通讯作者:
Meyle, Joerg
Meyle, Joerg
中科院分区:
医学4区
文献类型:
--
作者:
Groeger, Sabine;Domann, Eugen;Meyle, Joerg

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宿主细胞中B7-H1受体的上调可能会影响炎症性疾病的慢性化,这些炎症性疾病通常先于人类癌症的发展。在大多数人类癌症中检测到B7-H1表达,导致活化T细胞的无反应性和凋亡,并使肿瘤细胞能够克服宿主反应。牙龈卟啉单胞菌(Porphyromonas gingivalis,P. gingivalis)是牙周炎的病原菌,表达多种毒力因子。本研究以两株牙龈卟啉单胞菌(P. gingivalis,P. gingivalis)为研究对象,分析了B7-H1和B7-DC受体在口腔鳞癌细胞SCC-25和BHY以及原代人牙龈角质形成细胞(PHGK)中的表达。48小时后,将细胞用人B7-H1和B7-DC的抗体染色,并通过流式细胞术进一步分析。提取RNA并通过真实的时间PCR定量B7-H1或B7-DC的基因表达。牙龈卟啉单胞菌感染后,B7-H1和B7-DC受体均上调。在SCC-25细胞中,平均荧光强度(MFI)从4.5增加到9.9(B7-H1)和从6.9增加到15.0(B7-DC)(分别为p < 0.05)。PHGK显示从4.8增加到12.4(B7-H1)和从5.5增加到15.6(B7-DC)(分别为p < 0.05)。唾液链球菌K12,一种肠道细菌,没有引起上调。24小时后,在感染的细胞中B7 H1和B7-DC mRNA的表达,标准化为GAPDH和相对于未感染的细胞,是6.4倍(B7-H1)和8.6倍(B7-DC)。在PHGK中,B7-H1/DC mRNA表达分别增加8.2倍(B7-H1)和5.9倍(B7 DC)(p < 0.05)。研究结果表明,与S.唾液链球菌K12强毒牙龈卟啉单胞菌菌株能够诱导鳞状癌细胞和人牙龈角质形成细胞中B7-H1和B7-DC受体的表达,这可能促进口腔癌的免疫逃避。(C)2011年Elsevier GmbH。All rights reserved.
The up-regulation of the B7-H1 receptors in host cells might influence the chronicity of inflammatory disorders that frequently precede the development of human cancers. B7-H1 expression has been detected in the majority of human cancers, leading to anergy and apoptosis of activated T cells, and enabling tumor cells to overcome host response. Porphyromonas gingivalis (P. gingivalis), a putative periodontal pathogen, is an etiologic agent of periodontitis and expresses a variety of virulence factors. In this study, the expression of B7-H1 and B7-DC receptors on squamous cell carcinoma cells SCC-25 and BHY and primary human gingival keratinocytes (PHGK) was analyzed after infection with two virulent P. gingivalis strains in vitro. After 48 h, the cells were stained with antibodies for human B7-H1 and B7-DC and further analyzed by flow cytometry. RNA was extracted and gene expression of B7-H1 or B7-DC was quantified by real time PCR. After infection with P. gingivalis, both B7-H1 and B7-DC receptors were up-regulated. The mean fluorescence intensity (MFI) increased from 4.5 to 9.9 (B7-H1) and from 6.9 to 15.0 (B7-DC) (p < 0.05, respectively) in SCC-25 cells. PHGK showed an increase from 4.8 to 12.4 (B7-H1) and from 5.5 to 15.6 (B7-DC) (p < 0.05, respectively). Streptococcus salivarius K12, a commensal bacterium, caused no up-regulation. After 24 h, the expression of B7H1 and B7-DC mRNA in infected cells, normalized to GAPDH and in relation to non-infected cells, was 6.4 fold (B7-H1) and 8.6 fold (B7-DC) higher. In PHGK B7-H1/DC mRNA expression increased 8.2 fold (B7-H1) and 5.9 fold (B7DC) (p < 0.05) respectively. The results of the study demonstrate that in contrast to S. salivarius K12 virulent P. gingivalis strains are able to induce the expression of the B7-H1 and B7-DC receptors in squamous carcinoma cells and human gingival keratinocytes, which might facilitate immune evasion by oral cancers. (C) 2011 Elsevier GmbH. All rights reserved.