Interplay of protease-activated receptors and NOD pattern recognition receptors in epithelial innate immune responses to bacteria.
Interplay of protease-activated receptors and NOD pattern recognition receptors in epithelial innate immune responses to bacteria.
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DOI：
10.1016/j.imlet.2010.02.006
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发表时间：
2010-07-08
影响因子：
4.4
通讯作者：
DiJulio, Dennis H.
中科院分区：
文献类型：
--
作者：
Chung, Whasun O.;An, Jonathan Y.;Yin, Lei;Hacker, Beth M.;Rohani, Maryam G.;Dommisch, Henrik;DiJulio, Dennis H.
蛋白酶激活受体（PARs）、核苷酸结合寡聚化结构域（NOD）受体和Toll样受体（TLR）在先天免疫中发挥作用，但这些受体之间的相互作用知之甚少。本研究的目的是研究沉默一种受体如何影响其他受体和下游先天免疫标记物对细菌的反应。人牙龈上皮细胞（GEC）用PAR 1或PAR 2特异性siRNA转染，然后用牙周病原体牙龈卟啉单胞菌（Porphyromonas gingivalis）刺激，所述牙龈卟啉单胞菌是病原体和非病原体具核梭杆菌（Fusobacterium nucleatum）或非病原体戈登链球菌（Streptococcus gordonii）之间的桥接生物。PAR 1或PAR 2基因敲低导致NOD 1和NOD 2表达上调，牙龈卟啉单胞菌或F.细胞核刺激（p<0.01），以及当细胞分别被利用TLR2或TLR4的细菌刺激时增强的TLR2和TLR4表达。参与PAR的诱导CC趋化因子配体20（CCL20），一种细胞因子与抗微生物特性，观察后刺激的三种细菌物种。此外，来自多种细胞因子ELISA阵列的结果显示，用于诱导各种先天免疫标志物的受体是针对所测试的个体细菌定制的。我们的数据表明，对口腔内存在的不同类型细菌的适当先天免疫反应需要几种受体的复杂相互作用，并且受体表达本身会根据细胞遇到的生物体而改变。
Protease-Activated Receptors (PARs), Nucleotide-binding Oligomerization Domain (NOD) receptors and Toll-like receptors (TLRs) play a role in innate immunity, but little is known about interaction between these receptors. The goal of this study was to investigate how silencing one receptor affects the expression of other receptors and downstream innate immune markers in response to bacteria. Human gingival epithelial cells (GECs) were transfected with siRNA specific for PAR1 or PAR2, then stimulated with periopathogen Porphyromonas gingivalis, bridging organism between pathogens and non-pathogens Fusobacterium nucleatum, or non-pathogen Streptococcus gordonii. PAR1 or PAR2 knock-down resulted in up-regulated NOD1 and NOD2 expression with P. gingivalis or F. nucleatum stimulation (p<0.01), as well as enhanced TLR2 and TLR4 expression when cells were stimulated by bacteria that utilize TLR2 or TLR4, respectively. Involvement of PARs for induction of CC chemokine ligand 20 (CCL20), a cytokine with antimicrobial properties, was observed following stimulation of the three bacterial species. Furthermore, results from multiple cytokine ELISA array showed receptors utilized in the induction of various innate immune markers are tailored to individual bacterium tested. Our data suggest complex interplay of several receptors is required for appropriate innate immune responses to the different types of bacteria present within the oral cavity and that receptor expression itself is altered depending on which organism the cell encounters.
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