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Synergistic mucus secretion by histamine and IL-4 through TMEM16A in airway epithelium

 Ju Wan Kang  ;  Yong Hyuk Lee  ;  Min Jeong Kang  ;  Hyun Jae Lee  ;  Ryung Oh  ;  Hyun Jin Min  ;  Wan Namkung  ;  Jae Young Choi  ;  Sang Nam Lee  ;  Chang-Hoon Kim  ;  Joo-Heon Yoon  ;  Hyung-Ju Cho 
 American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol.131(3) : L466-L476, 2017 
Journal Title
 American Journal of Physiology - Lung Cellular and Molecular Physiology 
Issue Date
Adult ; Animals ; Anoctamin-1 ; Cells, Cultured ; Chloride Channels/metabolism* ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Gene Expression Regulation/drug effects ; Histamine/pharmacology* ; Humans ; Interleukin-4/pharmacology* ; Ion Channel Gating/drug effects ; Models, Biological ; Mucus/secretion* ; Neoplasm Proteins/metabolism* ; Nose/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Histamine/genetics ; Receptors, Histamine/metabolism ; Respiratory Mucosa/drug effects ; Respiratory Mucosa/secretion* ; Rhinitis, Allergic/metabolism ; Rhinitis, Allergic/pathology ; Sus scrofa ; Trachea/pathology ; Turbinates/metabolism
IL-4 ; TMEM16A ; airway ; epithelium ; histamine ; mucus ; submucosal gland
Histamine is an important mediator of allergic reactions, and mucus hypersecretion is a major allergic symptom. However, the direct effect of histamine on mucus secretion from airway mucosal epithelia has not been clearly demonstrated. TMEM16A is a Ca2+-activated chloride channel, and it is closely related to fluid secretion in airway mucosal epithelia. We investigated whether histamine directly induces fluid secretion from epithelial cells or submucosal glands (SMG) and mechanisms related, therewith, in allergic airway diseases. In pig airway tissues from the nose or trachea, histamine was a potent secretagogue that directly induced strong responses. However, gland secretion from human nasal tissue was not induced by histamine, even in allergic rhinitis patients. Histamine type 1 receptor (H1R) and histamine type 2 receptor (H2R) were not noted in SMG by in situ hybridization. Cultured primary human nasal epithelial (NHE) cells were used for the measurement of short-circuit current changes with the Ussing chamber. Histamine-induced slight responses of anion secretions under normal conditions. The response was enhanced by IL-4 stimulation through TMEM16A, which might be related to fluid hypersecretion in allergic rhinitis. Pretreatment with IL-4 augmented the histamine response that was suppressed by a TMEM16A inhibitor. TMEM16A expression was enhanced by 24-h treatment of IL-4 in human nasal epithelial cells. The expression of TMEM16A was significantly elevated in an allergic rhinitis group, compared with a control group. We elucidated histamine-induced fluid secretions in synergy with IL-4 through TMEM16A in the human airway epithelium. In addition, we observed species differences between pigs and humans in terms of gland secretion of histamine.
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터)
Yonsei Authors
김창훈(Kim, Chang Hoon) ; 윤주헌(Yoon, Joo Heon) ; 이상남(Lee, Sang Nam) ; 조형주(Cho, Hyung Ju) ; 최재영(Choi, Jae Young)
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