Enhanced Goblet Cell Hyperplasia in HDC Knockout Mice with Allergic Airway Inflammation

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  • Yamauchi Kohei
    Third Department of Internal Medicine, Iwate Medical University School of Medicine
  • Piao Hong Mei
    Third Department of Internal Medicine, Iwate Medical University School of Medicine Department of Respiratory Medicine, Affiliated Hospital of Yanbian University College of Medicine
  • Nakadate Toshihide
    Third Department of Internal Medicine, Iwate Medical University School of Medicine
  • Shikanai Toshiki
    Third Department of Internal Medicine, Iwate Medical University School of Medicine
  • Nakamura Yutaka
    Third Department of Internal Medicine, Iwate Medical University School of Medicine
  • Ito Harumasa
    Third Department of Internal Medicine, Iwate Medical University School of Medicine
  • Mouri Takashi
    Third Department of Internal Medicine, Iwate Medical University School of Medicine
  • Kobayashi Hitoshi
    Third Department of Internal Medicine, Iwate Medical University School of Medicine
  • Maesawa Chihaya
    Second Department of Pathology, Iwate Medical University School of Medicine
  • Sawai Takashi
    First Department of Pathology, Iwate Medical University School of Medicine
  • Ohtsu Hiroshi
    Tohoku University Graduate School of Engineering
  • Inoue Hiroshi
    Third Department of Internal Medicine, Iwate Medical University School of Medicine

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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.<br> 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.<br> 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.<br> 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-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and IL-2 in the BALF all increased significantly in both groups compared to those exposed to saline. In particular, the concentration of TNF-α 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.<br> Conclusions: These results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.<br>

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