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Neutrophil Extracellular Traps Exert Potential Cytotoxic and Proinflammatory Effects in the Dental Pulp
Affiliation:1. Oral Biology, Birmingham Dental School and Hospital, College of Medical and Dental Sciences, Birmingham, United Kingdom;2. Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile;3. Instituto de Biología, Laboratorio de Microscopía Electrónica, Universidad de Valparaíso, Valparaíso, Chile;1. Division of Endodontics, University of Minnesota School of Dentistry, Minneapolis, Minnesota;2. Minnesota Dental Research Center for Biomaterials and Biomechanics, University of Minnesota School of Dentistry, Minneapolis, Minnesota;1. Department of Restorative Dentistry School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;2. Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;3. Clinical Research Unit, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil;4. Department of Specific Formation, School of Dentistry of Nova Friburgo, Fluminense Federal University, Nova Friburgo, Rio de Janeiro, Brazil;1. Postgraduate Program in Dentistry, Estácio de Sá University, Rio de Janeiro, Brazil;2. Postgraduate Program in Dental Sciences, Christus University, Fortaleza, Brazil;1. Division of Oral Biological Sciences, Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, Japan;2. Division of Oral Health, Growth and Development, Department of Pediatric Dentistry, Kyushu University Graduate School of Dental Science, Fukuoka, Japan;3. Kyushu University School of Dentistry, Fukuoka, Japan;1. Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas;2. Department of Endodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia;3. Department of Conservative Dentistry and Periodontology, University Hospital, Regensburg, Germany;4. Department of Oral Biology, Institute of Clinical Sciences, The University of Birmingham School of Dentistry, Birmingham, UK
Abstract:IntroductionNeutrophil extracellular traps (NETs) are an important innate immune mechanism aimed at limiting the dissemination of bacteria within tissues and localizing antibacterial killing mechanisms. There is significant interest in the role of NETs in a range of infectious and inflammatory diseases; however, their role in diseased pulp has yet to be explored. Our aim was to determine their relevance to infected pulp and how their components affect human dental pulp cell (HDPC) responses.MethodsDiseased pulp tissue was stained for the presence of extracellular DNA and elastase to detect the presence of NETs. Bacteria known to infect pulp were also assayed to determine their ability to stimulate NETs. Coculture studies and NET component challenge were used to determine the effect of extracellular NET release on HDPC viability and inflammatory response. NET-stimulated HDPC secretomes were assessed for their chemotactic activity for lymphocytes and macrophages.ResultsData indicate that NETs are present in infected pulp tissue and whole NETs, and their histone components, particularly H2A, decreased HDPC viability and stimulated chemokine release, resulting in an attraction of lymphocyte populations.ConclusionsNETs are likely important in pulpal pathogenesis with injurious and chronic inflammatory effects on HDPCs, which may contribute to disease progression. Macrophages are chemoattracted to NET-induced apoptotic HDPCs, facilitating cellular debris removal. NETs and histones may provide novel prognostic markers and/or therapeutic targets for pulpal diseases.
Keywords:Damage-associated molecular patterns  dentin-pulp complex  inflammation  polymorphonuclear leukocytes  pulp biology
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