title: Histamine regulates mucin expression through H1 receptor in airway epithelial cells.
abstract: CONCLUSIONS
  The data suggest that histamine up-regulates MUC2 gene regulation and mucin production in airway epithelial cells through histamine 1 receptor (H1R). Histamine appears to play an important role in the early phase of mucin regulation, which might be effectively blocked by an H1R antagonist.
  
  
  OBJECTIVE
  Histamine is an important inflammatory mediator during the early phase of allergic response and antihistamine is known to have an ability to reduce mucus secretion in inflamed airways. The goal of the present study was to determine the effects of histamine on MUC2 gene expression and mucin secretion and to investigate the response to histamine 1 receptor (H1R) blocker in NCI-H292 cells and HM3-MUC2 cells.
  
  
  METHODS
  NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, and HM3-MUC2 cells transfected with MUC2 promoter (-2,864/+19) pGL2 luciferase construct were used in the study. MUC2 mRNA expression was analyzed by RT-PCR for NCI-H292 cells and by luciferase assays for HM3-MUC2 cells. MUC2 protein production was determined by immunoassay and immunofluorescent stain in NCI-H292 cells.
  
  
  RESULTS
  Histamine increased MUC2 gene expression in a dose- and time-dependent manner. Peak response was reached at 12 h after histamine administration. MUC2 protein production was also dose-dependently increased, while it decreased with time in NCI-H292 cells. Pretreatment with histamine at a concentration of 1 mM induced MUC2 mRNAand protein production, which was equivalent to that caused by 10 µg/ml LPS, but less than that of 0.5 µM PMA. Histamine-induced MUC2 mRNA expression and mucin secretion were significantly suppressed by pretreatment with H1R antagonist.
authors.affiliation: Department of Otolaryngology, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
authors.forename: Hyoung-Mi
authors.initials: HM
authors.lastname: Kim
authors.forename: Chul Hee
authors.initials: CH
authors.lastname: Lee
authors.forename: Chae-Seo
authors.initials: CS
authors.lastname: Rhee
mesh_terms: D018277:Carcinoma, Mucoepidermoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055262:Mucin-2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D009077:Mucins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation
chemical_list: D017442:Histamine Agonists; D039563:Histamine H1 Antagonists, Non-Sedating; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D006632:Histamine