Enhanced goblet cell hyperplasia in HDC knockout mice with allergic airway inflammation.
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.
Yamauchi
Kohei
K
Third Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan. kyamauch@iwate-med.ac.jp
Piao
Hong Mei
HM
Nakadate
Toshihide
T
Shikanai
Toshiki
T
Nakamura
Yutaka
Y
Ito
Harumasa
H
Mouri
Takashi
T
Kobayashi
Hitoshi
H
Maesawa
Chihaya
C
Sawai
Takashi
T
Ohtsu
Hiroshi
H
Inoue
Hiroshi
H
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
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