Relationship between Calcium-Activated Chloride Channel 1 and MUC5AC in Goblet Cell Hyperplasia Induced by Interleukin-13 in Human Bronchial Epithelial Cells

Abstract

Background:Interleukin (IL)-13 has recently been reported as the major T-helper 2 cytokine involved in mucus overproduction and oversecretion in allergic airways. However, the relationship between human calcium-activated chloride channel-1 (hCLCA1) and MUC5AC induced by IL-13 in vitro has not been fully investigated. Objectives: The present study examines whether IL-13 induces the expression of hCLCA1 in normal human bronchial epithelial (NHBE) cells. We also investigated the relationship between hCLCA1 and MUC5AC expression and the development of goblet cell hyperplasia (GCH). Methods: NHBE cells were isolated from human bronchi, and cultured with an air-liquid interface. hCLCA1 and MUC5AC gene and protein expression, as well as GCH were examined in the cells after exposure to IL-13. Results: Incubation with IL-13 for 14 and 21 days increased the total number of epithelial cells, the number of periodic acid-Schiff (PAS)-stained epithelial cells, the number of goblet cells, as well as expression of mRNA and protein of hCLCA1 and MUC5AC. The number of goblet cells with secretory granules also increased after 21 days of incubation with IL-13. Niflumic acid, a chloride channel inhibitor, reduced mRNA expression of hCLCA1 and MUC5AC, and reduced the number of PAS-positive cells after incubation with IL-13. NHBE cells exposed or not to IL-13 expressed IL-13 receptor α₁ (IL-13Rα₁), and an antibody to IL-13 Rα₁ also reduced the number of PAS-positive cells after exposure to IL-13. Conclusions: IL-13 might induce the expression of MUC5AC and hCLCA1 gene and protein in well-differentiated NHBE cells. These cells might also differentiate into goblet cells and become hyperplastic.

Proteomic approach to identify candidate effector molecules during the in vitro immune exclusion of infectiveTeladorsagia circumcinctain the abomasum of sheep

“…Expression of hCLCA1 or mCLCA3 was found to be up-regulated following exposure to respiratory tract irritants that are responsible for a Th2 local inflammation [26,34]. It has been shown that at transcript and protein level, expression of hCLCA1 was up-regulated by IL-13 in normal human bronchial epithelial cells in vitro [33]. Whether the secretion of the ovine CLCA protein has a direct or indirect function in worm expulsion remains unknown, although hCLCA1 has been associated with an increase in mucus production following a Th2 response of the respiratory tract [34].…”

Modulation of mucus production by interleukin‐13 receptor α2 in the human airway epithelium

“…IL-13 induces the cell proliferation and goblet cell hyperplasia of human airway epithelial cells in vitro [7,8]. We previously reported that IL-13 induced MUC5AC expression with the development of goblet cell hyperplasia in human bronchial epithelial cells [9].…”

“…We previously demonstrated that IL-13 induces goblet cell hyperplasia in human airway epithelial cells via IL-13Rα 1 [9], but the role of IL-13Rα 2 on the IL-13-induced goblet cell hyperplasia remains to be elucidated.…”

“…The ethics committee of Shinshu University School of Medicine approved the study and the patients provided written informed consent to participate in all aspects of the investigation. The isolation and cultivation of normal human bronchial epithelial cells (NHBECs) have been previously reported [9]. Briefly, passage-2 NHBECs were seeded onto polyester inserts (Costar Transwell clear, Cambridge, MA).…”

“…After the NHBECs reached confluence (Day 0), medium containing IL-13 (recombinant human IL-13, BIOTEC, Hamburg, Germany) or vehicle (PBS) was added to basolateral side of the inserts, and the cells were incubated with 10 ng/ml of IL-13 [9] or vehicle (PBS) with the ALI method. The culture medium was changed every day, and the cells were incubated for 21 days with IL-13 or vehicle (PBS).…”