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Antimicrobial and immunomodulatory activity of host defense peptides,clavanins and LL-37, in vitro: An endodontic perspective
Affiliation:1. Curso de Odontologia, Universidade Católica de Brasília, Campus I, QS 07 Lote 01 EPCT, 71966-700, Águas Claras, Brasília, Distrito Federal, Brazil;2. Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Campus Avançado Asa Norte, SGAN 916 Módulo B Avenida W5, 70790-160, Brasília, Distrito Federal, Brazil;3. Programa de Doutorado da Rede Centro-Oeste, Universidade de Brasília, Campus Universitário Darcy Ribeiro, 70910-900, Brasília, DF, Brazil;4. Programa de Pós-Graduação em Ciências da Saúde, Universidade de Brasília, Brasília, DF, Brazil;5. Grupo de Engenharia Metabólica Aplicada a Bioprocessos, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF, Brazil;6. S-Inova Biotech, Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Av. Tamandaré, 6000, Jardim Seminário, 79117-900, Campo Grande, Mato Grosso do Sul, Brazil;7. Programa de Pós Graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Universidade Federal de Mato Grosso do Sul, Av. Costa e Silva, Cidade Universitária, 79070-900, Campo Grande, Mato Grosso do Sul, Brazil;1. Center for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, #232, 2259 Lower Mall Research Station, Vancouver, BC V6T 1Z4, Canada;1. Food Biological Manufacturing Laboratory, China Meat Research Center, Beijing 100068, China;2. Beijing Key Laboratory of Meat Processing Technology, Beijing 100068, China;1. Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198-6495, USA;2. Department of Physics, JNTUA College of Engineering, Anantapur 515002, India;1. Animal Molecular and Cellular Biology Graduate Program, University of Florida, Gainesville 32611;2. Department of Animal Sciences, University of Florida, Gainesville 32611
Abstract:Endodontic treatment is mainly based on root canal disinfection and its failure may be motivated by microbial resistance. Endodontic therapy can be benefitted by host defense peptides (HDPs), which are multifunctional molecules that act against persistent infection and inflammation. This study aimed to evaluate the antimicrobial, cytotoxic and immunomodulatory activity of several HDPs, namely clavanin A, clavanin A modified (MO) and LL-37, compared to intracanal medication Ca(OH)2. HDPs and Ca(OH)2 were evaluated by: (1) antimicrobial assays against Candida albicans and Enterococcus faecalis, (2) cytotoxicity assays and (3) cytokine tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1α, IL-6, IL-10 and IL-12 and nitric oxide (NO) production by RAW 264.7 cells incubated with or without heat-killed (HK) C. albicans or E. faecalis combined or not with interferon-γ. The minimum inhibitory concentration (MIC) was established only for E. faecalis (LL-37, 57 μM). Considering cytotoxicity, clavanin MO was able to reduce cell viability in many groups and demonstrated lowest LC50. The Ca(OH)2 up-regulated the production of MCP-1, TNF-α, IL-12 and IL-6 and down-regulated IL-1α, IL-10 and NO. Clavanins up-regulated the TNF-α and NO and down-regulated IL-10 production. LL-37 demonstrated up-regulation of IL-6 and TNF-α production and down-regulation in IL-10 and NO production. In conclusion, LL-37 demonstrated better antibacterial potential. In addition, Ca(OH)2 demonstrated a proinflammatory response, while the HDPs modulated the inflammatory response from non-interference with the active cytokines in the osteoclastogenesis process, probably promoting the health of periradicular tissues.
Keywords:Cytokines  Endodontics  Host defense peptide
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