title: Identification of signaling pathways in macrophage exposed to Porphyromonas gingivalis or to its purified cell wall components.
abstract: Porphyromonas gingivalis (P. gingivalis) can trigger an inflammatory condition leading to the destruction of periodontal tissues. However P. gingivalis LPS and its fimbriae (FimA) play different roles compared with the live bacteria in the context of intracellular molecule induction and cytokine secretion. To elucidate whether this difference results from different signaling pathways in host immune response to P. gingivalis, its LPS, or its FimA, we examined gene expression profile of human macrophages exposed to P. gingivalis, its LPS, or its FimA. A comparison of gene expression resulted in the identification of three distinct groups of expressed genes. Furthermore, computer-assisted promoter analysis of a subset of each group of differentially regulated genes revealed four putative transcriptional regulation models that associate with transcription factors NFkappaB, IRF7, and KLF4. Using gene knockout mice and siRNA to silence mouse genes, we showed that both TLR2 and TLR7 are essential for the induction of NFkappaB-containing genes and NFkappaB-IFN-sensitive response element (ISRE) cocontaining genes by either P. gingivalis or its purified components. The gene induction via either TLR2 or TLR7 is dependent on both MyD88 and p38 MAPK. However, the unique induction of IFN-beta by P. gingivalis LPS requires TLR7 and IFNalphabetaR cosignaling, and the induction of ISRE-containing gene is dependent on the activation of IFN-beta autocrine loop. Taken together, these data demonstrate that P. gingivalis and its components induce NFkappaB-containing genes through either TLR2- or TLR7-MyD88-p38 MAPK pathway, while P. gingivalis LPS uniquely induces ISRE-containing genes, which requires IFNalphabetaR signaling involving IRF7, KLF4, and pY701 STAT1.
authors.affiliation: Department of Periodontology and Oral Biology, School of Dental Medicine, Boston University, Boston, MA 02118, USA.
authors.forename: Qingde
authors.initials: Q
authors.lastname: Zhou
authors.forename: Salomon
authors.initials: S
authors.lastname: Amar
mesh_terms: D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology*; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology*; D036781:Fimbriae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D000090062:Kruppel-Like Factor 4; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D016966:Porphyromonas gingivalis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D053633:Receptor, Interferon alpha-beta / Q000276:immunology; D020218:Response Elements / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D034741:RNA, Small Interfering; C493486:Tlr2 protein, mouse; C477038:Tlr7 protein, mouse; D051195:Toll-Like Receptor 2; D051199:Toll-Like Receptor 7; C063055:fimbrillin; D036781:Fimbriae Proteins; D053633:Receptor, Interferon alpha-beta; D048051:p38 Mitogen-Activated Protein Kinases