title: Propolis modulates miRNAs involved in TLR-4 pathway, NF-κB activation, cytokine production and in the bactericidal activity of human dendritic cells.
abstract: OBJECTIVE
  Dendritic cells (DCs) are antigen-presenting cells, essential for recognition and presentation of pathogens to T cells. Propolis, a resinous material produced by bees from various plants, exhibits numerous biological properties, highlighting its immunomodulatory action. Here, we assayed the effects of propolis on the maturation and function of human DCs.
  
  
  METHODS
  DCs were generated from human monocytes and incubated with propolis and LPS. NF-κB and cytokines production were determined by ELISA. microRNA's expression was analysed by RT-qPCR and cell markers detection by flow cytometry. Colony-forming units were obtained to assess the bactericidal activity of propolis-treated DCs.
  
  
  RESULTS
  Propolis activated DCs in the presence of LPS, inducing NF-kB, TNF-α, IL-6 and IL-10 production. The inhibition of hsa-miR-148a and hsa-miR-148b abolished the inhibitory effects on HLA-DR and pro-inflammatory cytokines. The increased expression of hsa-miR-155 may be correlated to the increase in TLR-4 and CD86 expression, maintaining LPS-induced expression of HLA-DR and CD40. Such parameters may be involved in the increased bactericidal activity of DCs against Streptococcus mutans.
  
  
  CONCLUSIONS
  Propolis modulated the maturation and function of DCs and may be useful in the initial steps of the immune response, providing a novel approach to the development of DC-based strategies and for the discovery of new immunomodulators.
authors.affiliation: Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University (UNESP), São Paulo, Brazil.
authors.forename: Bruno J
authors.initials: BJ
authors.lastname: Conti
authors.affiliation: Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University (UNESP), São Paulo, Brazil.
authors.forename: Karina B
authors.initials: KB
authors.lastname: Santiago
authors.affiliation: Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University (UNESP), São Paulo, Brazil.
authors.forename: Eliza O
authors.initials: EO
authors.lastname: Cardoso
authors.affiliation: Department of Morphology, Biosciences Institute, São Paulo State University (UNESP), São Paulo, Brazil.
authors.forename: Paula P
authors.initials: PP
authors.lastname: Freire
authors.affiliation: Department of Morphology, Biosciences Institute, São Paulo State University (UNESP), São Paulo, Brazil.
authors.forename: Robson F
authors.initials: RF
authors.lastname: Carvalho
authors.affiliation: Botucatu Blood Center, School of Medicine, São Paulo State University (UNESP), São Paulo, Brazil.
authors.forename: Marjorie A
authors.initials: MA
authors.lastname: Golim
authors.affiliation: Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University (UNESP), São Paulo, Brazil.
authors.forename: José M
authors.initials: JM
authors.lastname: Sforcin
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D006684:HLA-DR Antigens / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D011429:Propolis / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013295:Streptococcus mutans / Q000276:immunology / Q000472:pathogenicity*; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D016207:Cytokines; D006684:HLA-DR Antigens; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; C550570:MIRN148 microRNA, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D011429:Propolis
keywords: dendritic cells; immunomodulation; propolis