title: Enhanced goblet cell hyperplasia in HDC knockout mice with allergic airway inflammation.
abstract: BACKGROUND
  Histamine is known to have immunoregulatory roles in allergic reactions through histamine receptor 1 (H1R), H2R, H3R and H4R. However, its role in goblet cell hyperplasia in the airways of asthma patients is yet to be clarified.
  
  
  OBJECTIVE
  This study was designed to examine the role of histamine in goblet cell hyperplasia using histamine-deficient mice (Hdc-/- mice) with allergic airway inflammation.
  
  
  METHODS
  Wild-type and Hdc-/- C57BL/6 mice were sensitized with ovalbumin (OVA). After a 2-week exposure to OVA, goblet cell hyperplasia was evaluated. Cell differentials and cytokines in BALF were analyzed. The mRNA levels of MUC5AC and Gob-5 gene were determined quantitatively.
  
  
  RESULTS
  The number of eosinophils in BALF increased in both the sensitized wild-type mice and Hdc-/- mice with OVA inhalation. In addition, the numbers of alveolar macrophages and lymphocytes in BALF increased significantly in the sensitized Hdc-/- mice with OVA inhalation compared to the wild-type mice under the same conditions. The concentrations of Interleukin-4 (IL-4), IL-5, IL-13, Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and IL-2 in the BALF all increased significantly in both groups compared to those exposed to saline. In particular, the concentration of TNF-alpha in the Hdc-/- mice exposed to OVA was significantly higher than that in the wild-type mice under the same conditions. The mRNA levels of Gob-5 and MUC5AC, and the ratio of the goblet cells in the airway epithelium significantly increased in Hdc-/- mice exposed to OVA compared to wild-type mice.
  
  
  CONCLUSIONS
  These results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.
authors.affiliation: Third Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan. kyamauch@iwate-med.ac.jp
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Hong Mei
authors.initials: HM
authors.lastname: Piao
authors.forename: Toshihide
authors.initials: T
authors.lastname: Nakadate
authors.forename: Toshiki
authors.initials: T
authors.lastname: Shikanai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Harumasa
authors.initials: H
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Mouri
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Chihaya
authors.initials: C
authors.lastname: Maesawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Sawai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000818:Animals; D001249:Asthma / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002454:Cell Differentiation; D018118:Chloride Channels / Q000235:genetics; D016207:Cytokines / Q000032:analysis; D005260:Female; D020397:Goblet Cells / Q000473:pathology*; D006632:Histamine / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000502:physiology; D006965:Hyperplasia; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055271:Mucin 5AC / Q000235:genetics; D009088:Mucoproteins / Q000235:genetics
chemical_list: D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D016207:Cytokines; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009088:Mucoproteins; D007073:Immunoglobulin E; D006632:Histamine; D006640:Histidine Decarboxylase