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-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. Conclusions: These results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.

Keywords

• airway remodeling
• asthma
• Gob-5
• MUC5AC
• TNF-α