牙龈卟啉单胞菌刺激树突状细胞激活炎症反应
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摘要
目的分析树突状细胞在牙龈卟啉单胞菌感染后的差异表达基因,探讨牙周炎的致病机制。方法利用高通量测序技术分析体外诱导分化的树突状细胞在牙龈卟啉单胞菌感染情况下的差异基因表达、基因集及相关功能。结果本实验总计发现7 305个至少有两倍变化的差异表达基因。基因本体结果显示牙龈卟啉单胞菌感染后树突状细胞的生物过程、细胞成份、分子功能均发生较大变化。基因集富集分析结果显示肿瘤坏死因子基因集、细胞因子及炎症反应基因集、白介素1及转录因子NF-k B家族基因集、干扰素信号基因集、B细胞受体信号基因集、T细胞受体信号基因集富集明显。结论树突状细胞在牙龈卟啉单胞菌感染后会导致基因水平的变化,引起机体免疫反应及炎症反应的发生,趋化因子配体(Chemokine(C-X-C motif)ligand,CXCL)及细胞因子信号抑制物(Suppressor of cytokine signaling,SOCS)的水平及作用可作为日后研究的方向。
Objective To analyze differentially expressed genes of dendritic cells infected with Porhyromonas gingivalis( P.gingivalis),to explore the pathogenesis of periodontitis. Methods High-throughput sequencing was used to analyze differentially expressed genes,gene pools and related functions of in vitro induced dendritic cells under P. gingivalis infection. Results A total of 7305 differentially expressed genes with at least two-fold changes were found in this experiment. The results of gene ontology showed that the biological processes,cell components,and molecular functions of dendritic cells after P. gingivalis infection greatly changed. Gene enrichment analysis showed that the tumor necrosis factor gene set,cytokine and inflammatory response gene set,interleukin 1 and NF-k B family of gene transcription factor,interferon signal gene set,B cell receptor signal gene set,T cell receptor signal gene set were enriched significantly. Conclusions Dendritic cells can cause genetic changes after P. gingivalis infection,causing the immune response and inflammatory reaction. The levels and effects of CXCL and SOCS can be the direction of future research.
Objective To analyze differentially expressed genes of dendritic cells infected with Porhyromonas gingivalis( P.gingivalis),to explore the pathogenesis of periodontitis. Methods High-throughput sequencing was used to analyze differentially expressed genes,gene pools and related functions of in vitro induced dendritic cells under P. gingivalis infection. Results A total of 7305 differentially expressed genes with at least two-fold changes were found in this experiment. The results of gene ontology showed that the biological processes,cell components,and molecular functions of dendritic cells after P. gingivalis infection greatly changed. Gene enrichment analysis showed that the tumor necrosis factor gene set,cytokine and inflammatory response gene set,interleukin 1 and NF-k B family of gene transcription factor,interferon signal gene set,B cell receptor signal gene set,T cell receptor signal gene set were enriched significantly. Conclusions Dendritic cells can cause genetic changes after P. gingivalis infection,causing the immune response and inflammatory reaction. The levels and effects of CXCL and SOCS can be the direction of future research.
引文
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[13]Dodo CG,Meirelles L,Aviles-Reyes A,et al.Pro-inflammatory analysis of macrophages in contact with titanium particles and porphyromonas gingivalis[J].Braz Dent J,2017,28(4):428-434.
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[15]Ren H,Li Y,Jiang H,et al.Porphyromonas gingivalis induces IL-8 and IFN-gamma secretion and apoptosis in human extravillous trophoblast derived HTR8/SVneo cells via activation of ERK1/2and p38 signaling pathways[J].Placenta,2016,45:8-15.
[16]Andia DC,Planello AC,Portinho D,et al.DNA methylation analysis of SOCS1,SOCS3,and LINE-1 in microdissected gingival tissue[J].Clin Oral Investig,2015,19(9):2337-2344.
[17]Tew JG,El Shikh ME,RM.El Sayed,et al.Dendritic cells,antibodies reactive with ox LDL,and inflammation[J].J Dent Res,2012,91(1):8-16.
[18]Teng YT,Mahamed D,Singh B.Gamma interferon positively modulates Actinobacillus actinomycetemcomitans-specific RANKL+CD4+Th-cell-mediated alveolar bone destruction in vivo[J].Infect Immun,2005,73(6):3453-3461.
[19]Chen W,Gao B,Hao L,et al.The silencing of cathepsin K used in gene therapy for periodontal disease reveals the role of cathepsin K in chronic infection and inflammation[J].J Periodontal Res,2016,51(5):647-660.
[20]Schallhorn RA,Patel DN,Chandrasekar B,et al.Periodontal disease in association with systemic levels of interleukin-18 and CXC ligand 16 in patients undergoing cardiac catheterization[J].J Periodontol,2010,81(8):1180-1186.
[21]Hosokawa I,Hosokawa Y,Shindo S,et al.Melatonin inhibits CXCL10 and MMP-1 production in IL-1beta-stimulated human periodontal ligament Cells[J].Inflammation,2016,39(4):1520-1526.
[22]Xiao W,Dong G,Pacios S,et al.FOXO1 deletion reduces dendritic cell function and enhances susceptibility to periodontitis[J].Am J Pathol,2015,185(4):1085-1093.
[2]王畅,唐子圣,漆正楠,等.感染根管中牙龈卟啉单胞菌fim A基因多态性研究[J].口腔医学,2016,36(1):18-21,33.
[3]Akca K,Akkocaoglu M,Comert A,et al.Bone strains around immediately loaded implants supporting mandibular overdentures in human cadavers[J].Int J Oral Maxillofac Implants,2007,22(1):101-109.
[4]Song L,Dong G,Guo L,et al.The function of dendritic cells in modulating the host response[J].Mol Oral Microbiol,2017,00:1-9.
[5]Oda T,Yoshie H,Yamazaki K.Porphyromonas gingivalis antigen preferentially stimulates T cells to express IL-17 but not receptor activator of NF-kappa B ligand in vitro[J].Oral Microbiol Immunol,2003,18(1):30-36.
[6]Larsen JM.The immune response to Prevotella bacteria in chronic inflammatory disease[J].Immunology,2017,151(4):363-374.
[7]Bradley JH,Stein R,Randolph B,et al.T cell resistance to activation by dendritic cells requires long-term culture in simulated microgravity[J].Life Sci Space Res(Amst),2017,15:55-61.
[8]Retamal-Diaz A,Weiss KA,Tognarelli EI,et al.US6 gene deletion in herpes simplex virus type 2 enhances dendritic cell function and T cell activation[J].Front Immunol,2017,8:1523.
[9]Vlasenko R,Stepanenko RN,Koval'chuk LV.Regulation by myelopid of immunoglobulin production in culture of human peripheral blood lymphocytes in normal and secondary immuno deficient state[J].Biull Eksp Biol Med,1990,110(8):180-182.
[10]Arjunan P,El-Awady A,Dannebaum RO,et al.High-throughput sequencing reveals key genes and immune homeostatic pathways activated in myeloid dendritic cells by Porphyromonas gingivalis381 and its fimbrial mutants[J].Mol Oral Microbiol,2016,31(1):78-93.
[11]El-Awady AR,Miles B,Scisci E,et al.Porphyromonas gingivalis evasion of autophagy and intracellular killing by human myeloid dendritic cells involves DC-SIGN-TLR2 crosstalk[J].PLo S Pathog,2015,10(2):e1004647.
[12]Song L,Yao J,He Z,et al.Genes related to inflammation and bone loss process in periodontitis suggested by bioinformatics methods[J].BMC Oral Health,2015,15:105.
[13]Dodo CG,Meirelles L,Aviles-Reyes A,et al.Pro-inflammatory analysis of macrophages in contact with titanium particles and porphyromonas gingivalis[J].Braz Dent J,2017,28(4):428-434.
[14]Wang HY,Lin L,Fu W,et al.Preventive effects of the novel antimicrobial peptide Nal-P-113 in a rat Periodontitis model by limiting the growth of Porphyromonas gingivalis and modulating IL-1beta and TNF-alpha production[J].BMC Complement Altern Med,2017,17(1):426.
[15]Ren H,Li Y,Jiang H,et al.Porphyromonas gingivalis induces IL-8 and IFN-gamma secretion and apoptosis in human extravillous trophoblast derived HTR8/SVneo cells via activation of ERK1/2and p38 signaling pathways[J].Placenta,2016,45:8-15.
[16]Andia DC,Planello AC,Portinho D,et al.DNA methylation analysis of SOCS1,SOCS3,and LINE-1 in microdissected gingival tissue[J].Clin Oral Investig,2015,19(9):2337-2344.
[17]Tew JG,El Shikh ME,RM.El Sayed,et al.Dendritic cells,antibodies reactive with ox LDL,and inflammation[J].J Dent Res,2012,91(1):8-16.
[18]Teng YT,Mahamed D,Singh B.Gamma interferon positively modulates Actinobacillus actinomycetemcomitans-specific RANKL+CD4+Th-cell-mediated alveolar bone destruction in vivo[J].Infect Immun,2005,73(6):3453-3461.
[19]Chen W,Gao B,Hao L,et al.The silencing of cathepsin K used in gene therapy for periodontal disease reveals the role of cathepsin K in chronic infection and inflammation[J].J Periodontal Res,2016,51(5):647-660.
[20]Schallhorn RA,Patel DN,Chandrasekar B,et al.Periodontal disease in association with systemic levels of interleukin-18 and CXC ligand 16 in patients undergoing cardiac catheterization[J].J Periodontol,2010,81(8):1180-1186.
[21]Hosokawa I,Hosokawa Y,Shindo S,et al.Melatonin inhibits CXCL10 and MMP-1 production in IL-1beta-stimulated human periodontal ligament Cells[J].Inflammation,2016,39(4):1520-1526.
[22]Xiao W,Dong G,Pacios S,et al.FOXO1 deletion reduces dendritic cell function and enhances susceptibility to periodontitis[J].Am J Pathol,2015,185(4):1085-1093.