title: Brain-derived neurotrophic factor prevents the endothelial barrier dysfunction induced by interleukin-1β and tumor necrosis factor-α.
abstract: OBJECTIVE
  Brain-derived neurotrophic factor (BDNF) promotes the regeneration of periodontal tissue. Although a local inflammatory step is required to initiate the subsequent process of tissue regeneration, excessive inflammation may inhibit or delay tissue regeneration. Therefore, the regulation of inflammation is essential for periodontal tissue regeneration. In the present study, we examined the influence of BDNF on the human microvascular endothelial cell (HMVEC) barrier dysfunction induced by interleukin (IL)-1β or tumor necrosis factor (TNF)-α to determine the effects of BDNF on the regulation of local inflammation in periodontal tissue regeneration.
  
  
  METHODS
  Endothelial permeability was analyzed using a Dextran transport assay with transwell plates. The expression of vascular endothelial (VE)-cadherin was assessed by immunoblotting and immunofluorescence microscopy.
  
  
  RESULTS
  BDNF (25 ng/mL) inhibited increase induced in endothelial permeability by IL-1β and TNF-α. IL-1β and TNF-α decreased VE-cadherin protein levels, while BDNF recovered the reduction in HMVECs. BDNF protected the increase induced in endothelial permeability by IL-1β and TNF-α through TrkB. The single addition of BDNF into the culture increased the expression of VE-cadherin in HMVECs.
  
  
  CONCLUSIONS
  BDNF played an important role in inhibiting endothelial barrier dysfunction, which suggests that it may assist in enhancing periodontal tissue regeneration.
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kajiya
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kashiwai
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shiba
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D015703:Antigens, CD / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D015820:Cadherins / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D003911:Dextrans; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005456:Fluorescent Dyes; D006801:Humans; D015151:Immunoblotting; D026121:Indole Alkaloids / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D020813:Receptor, trkB / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D019208:Brain-Derived Neurotrophic Factor; D015820:Cadherins; D002227:Carbazoles; D003911:Dextrans; D004791:Enzyme Inhibitors; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D026121:Indole Alkaloids; D053583:Interleukin-1beta; D020813:Receptor, trkB; D014409:Tumor Necrosis Factor-alpha; D000099152:Cadherin 5; C015219:fluorescein isothiocyanate dextran; C049985:staurosporine aglycone
keywords: brain-derived neurotrophic factor; endothelial cell permeability; inflammatory cytokine; periodontal tissue regeneration