title: Treponema denticola activates mitogen-activated protein kinase signal pathways through Toll-like receptor 2.
abstract: Treponema denticola, a spirochete indigenous to the oral cavity, is associated with host inflammatory responses to anaerobic polymicrobial infections of the root canal, periodontium, and alveolar bone. However, the cellular mechanisms responsible for the recognition of T. denticola by the innate immune system and the underlying cell signaling pathways that regulate the inflammatory response to T. denticola are currently unresolved. In this study, we demonstrate that T. denticola induces innate immune responses via the utilization of Toll-like receptor 2 (TLR2) but not TLR4. Assessment of TLR2/1 and TLR2/6 heterodimers revealed that T. denticola predominantly utilizes TLR2/6 for the induction of cellular responses. Analysis of the mitogen-activated protein kinase (MAPK) signaling pathway in T. denticola-stimulated monocytes identified a prolonged up-regulation of the MAPK extracellular signal-related kinase 1/2 (ERK1/2) and p38, while no discernible increase in phospho-c-Jun N-terminal kinase 1/2 (JNK1/2) levels was observed. With the aid of pharmacological inhibitors selectively targeting ERK1/2 via the mitogen-activated protein kinase/extracellular signal-related kinase 1/2 kinase and p38, we further demonstrate that ERK1/2 and p38 play a major role in T. denticola-mediated pro- and anti-inflammatory cytokine production.
authors.affiliation: Department of Pediatric Dentistry, School of Dentistry, SDB 314, 1530 3rd Ave. S., The University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA. john_ruby@cs1.dental.uab.edu
authors.forename: John
authors.initials: J
authors.lastname: Ruby
authors.forename: Kunal
authors.initials: K
authors.lastname: Rehani
authors.forename: Michael
authors.initials: M
authors.lastname: Martin
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000276:immunology; D048373:Treponema denticola / Q000276:immunology*; D014211:Treponemal Infections / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases