Aging and contribution of MyD88 and TRIF to expression of TLR pathway-associated genes following stimulation with Porphyromonas gingivalis.
Aging and contribution of MyD88 and TRIF to expression of TLR pathway-associated genes following stimulation with Porphyromonas gingivalis.
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DOI：
10.1111/jre.12185
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发表时间：
2015-02
影响因子：
3.5
通讯作者：
Gibson FC 3rd
中科院分区：
文献类型：
--
作者：
Shaik-Dasthagirisaheb YB;Huang N;Weinberg EO;Shen SS;Genco CA;Gibson FC 3rd
牙周病是一种高度复杂的口腔慢性炎症性疾病。多种因素影响牙周病，包括社会经济地位、遗传、年龄，然而，由龈下间隙存在的特定细菌引起的炎症被认为是导致大多数软硬组织破坏的原因。牙龈卟啉单胞菌与牙周病密切相关。toll样受体（TLRs）及其胞内信号通路在宿主对牙龈假单胞菌的应答中起重要作用。本研究的重点是利用微阵列分析确定TLR接头分子MyD88和TRIF以及衰老对牙龈假单胞菌TLR通路相关mRNA表达的贡献。用牙龈假单胞菌培养野生型（Wt）、MyD88-KO和TrifLps2小鼠2月龄和12月龄的骨髓来源巨噬细胞（BMØ）。与单独培养基对照比较，测定牙龈假单胞菌培养BMØ中基因的表达。利用mRNA表达标准的两倍截断，将2月龄小鼠与牙龈假单胞菌一起培养Wt BMØ与单独培养基对照相比，观察到32个基因的差异表达。与2月龄Wt相比，MyD88和TRIF突变分别导致21个和12个基因差异表达（P<0.05）。Wt BMØ经牙龈假单胞菌培养后，12个月组5个基因的表达量较2个月组显著降低（P<0.05）。年龄也影响MyD88-KO和TrifLps2小鼠的基因表达。我们的研究结果表明，牙龈假单胞菌诱导TLR通路相关基因的差异表达，MyD88和TRIF都参与了这些基因的表达。年龄也在牙龈假单胞菌刺激BMØ后tlr相关基因的表达中起作用。
Periodontal disease is a highly complex chronic inflammatory disease of the oral cavity. Multiple factors influence periodontal disease including socioeconomic status, genetics, age, however, inflammation elicited by the presence of specific bacteria in the subgingival space is thought to drive the majority of soft and hard tissue destruction. Porphyromonas gingivalis is closely associated with periodontal disease. Toll-like receptors (TLRs) and their intracellular signaling pathways play roles in host responses to P. gingivalis. The focus of current study was to use microarray analysis to define the contributions that TLR adaptor molecules MyD88 and TRIF, and aging have on TLR pathway associated mRNA expression in response to P. gingivalis. Bone marrow derived macrophages (BMØ) from wild type (Wt), MyD88-KO and TrifLps2 mice at 2-months and 12-months of age were cultured with P. gingivalis. Expression of genes in BMØ cultured with P. gingivalis was determined in comparison to medium alone control. Using a two-fold cut-off in mRNA expression criteria, differential expression of 32 genes was observed when Wt BMØ from 2-month old mice were cultured with P. gingivalis compared with medium alone control. When compared with 2-month old Wt, 21 and 12 genes were differentially expressed (P<0.05) as a result of MyD88 or TRIF mutations respectively. The expression of 5 genes was significantly (P<0.05) reduced in the 12-month group compared to the 2-month group in Wt BMØ following culture with P. gingivalis. Age also influenced expression of genes in MyD88-KO and TrifLps2 mice challenged with P. gingivalis. Our results indicate that P. gingivalis induces differential expression of TLR pathway associated genes, and both MyD88, and TRIF play roles in the expression of these genes. Age also played a role in the expression of TLR-associated genes following stimulation of BMØ with P. gingivalis.
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