title: Bile acid increases expression of the histamine-producing enzyme, histidine decarboxylase, in gastric cells.
abstract: OBJECTIVE
  To investigate the effect of bile acid on the expression of histidine decarboxylase (HDC), which is a major enzyme involved in histamine production, and gene expression of gastric transcription factors upon cooperative activation.
  
  
  METHODS
  HDC expression was examined by immunohistochemistry, reverse transcriptase polymerase chain reaction, and promoter assay in human gastric precancerous tissues, normal stomach tissue, and gastric cancer cell lines. The relationship between gastric precancerous state and HDC expression induced by bile acid was determined. The association between the expression of HDC and various specific transcription factors in gastric cells was also evaluated. MKN45 and AGS human gastric carcinoma cell lines were transfected with farnesoid X receptor (FXR), small heterodimer partner (SHP), and caudal-type homeodomain transcription factor (CDX)1 expression plasmids. The effects of various transcription factors on HDC expression were monitored by luciferase-reporter promoter assay.
  
  
  RESULTS
  Histamine production and secretion in the stomach play critical roles in gastric acid secretion and in the pathogenesis of gastric diseases. Here, we show that bile acid increased the expression of HDC, which is a rate-limiting enzyme of the histamine production pathway. FXR was found to be a primary regulatory transcription factor for bile acid-induced HDC expression. In addition, the transcription factors CDX1 and SHP synergistically enhanced bile acid-induced elevation of HDC gene expression. We confirmed similar expression patterns for HDC, CDX1, and SHP in patient tissues.
  
  
  CONCLUSIONS
  HDC production in the stomach is associated with bile acid exposure and its related transcriptional regulation network of FXR, SHP, and CDX1.
authors.affiliation: Hye Jin Ku, Hee Ju Park, Department of Pediatrics, College of Medicine, Pusan National University, Busan 601-721, South Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Ku
authors.affiliation: Hye Jin Ku, Hee Ju Park, Department of Pediatrics, College of Medicine, Pusan National University, Busan 601-721, South Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Hye Jin Ku, Hee Ju Park, Department of Pediatrics, College of Medicine, Pusan National University, Busan 601-721, South Korea.
authors.forename: Hyeong Hoe
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Hye Jin Ku, Hee Ju Park, Department of Pediatrics, College of Medicine, Pusan National University, Busan 601-721, South Korea.
authors.forename: Hee Ju
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Hye Jin Ku, Hee Ju Park, Department of Pediatrics, College of Medicine, Pusan National University, Busan 601-721, South Korea.
authors.forename: Jae Hun
authors.initials: JH
authors.lastname: Cheong
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism*; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006632:Histamine / Q000378:metabolism*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008679:Metaplasia; D011230:Precancerous Conditions / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D013270:Stomach / Q000201:enzymology* / Q000473:pathology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D006632:Histamine; D006640:Histidine Decarboxylase; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C491273:CDX1 protein, human; C099713:nuclear receptor subfamily 0, group B, member 2
keywords: Bile acid; Farnesoid X receptor; Histamine; Histidine decarboxylase