title: Stimulatory effects of histamine on migration of nasal fibroblasts.
abstract: BACKGROUND
  Fibroblast migration is crucial for normal wound repair after sinonasal surgery. Histamine is known to be involved in wound healing by its effects on cell proliferation and migration. This study aimed to determine whether histamine affects the migration of nasal fibroblasts and to investigate the mechanism of action of histamine on nasal fibroblasts.
  
  
  METHODS
  Primary cultures of nasal fibroblasts were established from inferior turbinate samples. Fibroblast migration was evaluated with scratch assays. Cells were treated with histamine and/or histamine receptor-selective antagonists. U-73122 and pertussis toxin, which are selective inhibitors of the lower signaling pathway of H1R and H4R, were used to confirm the modulation of nasal fibroblast migration by histamine. Fibroblast cytoskeletal structures were visualized with immunocytochemistry.
  
  
  RESULTS
  Histamine significantly stimulated the migration of nasal fibroblasts. Antagonists selective for HR1 and HR4 significantly reduced nasal fibroblast migration. In immunocytochemical staining, histamine treatment increased membrane ruffling and pyrilamine, diphenhydramine, fexofenadine, and JNJ7777120 decreased histamine-induced membrane ruffling. U-73122 and pertussis toxin also decreased histamine-induced migration of fibroblasts. Histamine maintains its stimulatory effects on fibroblast migration in the presence of mitomycin C, which blocks proliferation of cells.
  
  
  CONCLUSIONS
  We showed that histamine stimulates fibroblast migration in nasal fibroblasts. This effect appeared to be mediated by HR1 and HR4. However, because fibroblast migration also can be involved in scaring and fibrosis, more research is necessary to determine the effects of antihistamine on wound healing after sinus surgery.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Sung-Moon
authors.initials: SM
authors.lastname: Hong
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Il-Ho
authors.initials: IH
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, Korea University Graduate School, Korea University, Seoul, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Um
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Shin
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul, Korea.|Department of Biomedical Sciences, Korea University Graduate School, Korea University, Seoul, Korea.|Medical Devices Clinical Trial Center, Guro Hospital, Korea University, Seoul, Korea.
authors.forename: Heung-Man
authors.initials: HM
authors.lastname: Lee
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007114:Immunization; D007211:Indoles / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D015398:Signal Transduction / Q000187:drug effects; D014420:Turbinates / Q000166:cytology*
chemical_list: D004963:Estrenes; C418607:HRH4 protein, human; D007211:Indoles; D010879:Piperazines; D011760:Pyrrolidinones; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D006632:Histamine; D037342:Pertussis Toxin
keywords: histamine; histamine receptor; migration; nasal fibroblast; wound healing