Letter abstract

Nature Medicine 13, 862 - 867 (2007)
Published online: 24 June 2007 | doi:10.1038/nm1604

A GABAergic system in airway epithelium is essential for mucus overproduction in asthma

Yun-Yan Xiang1, Shuhe Wang2, Mingyao Liu3,4, Jeremy A Hirota5, Jingxin Li1,6, William Ju4, Yijun Fan2, Margaret M Kelly5, Bin Ye1, Beverley Orser4,7, Paul M O'Byrne5, Mark D Inman5, Xi Yang2 & Wei-Yang Lu1,4,7


gamma-Aminobutyric acid (GABA) is an important neurotransmitter that, through the subtype A GABA receptor (GABAAR), induces inhibition in the adult brain. Here we show that an excitatory, rather than inhibitory, GABAergic system exists in airway epithelial cells. Both GABAARs and the GABA synthetic enzyme glutamic acid decarboxylase (GAD) are expressed in pulmonary epithelial cells. Activation of GABAARs depolarized these cells. The expression of GAD in the cytosol and GABAARs in the apical membranes of airway epithelial cells increased markedly when mice were sensitized and then challenged with ovalbumin, an approach for inducing allergic asthmatic reactions. Similarly, GAD and GABAARs in airway epithelial cells of humans with asthma increased after allergen inhalation challenge. Intranasal application of selective GABAAR inhibitors suppressed the hyperplasia of goblet cells and the overproduction of mucus induced by ovalbumin or interleukin-13 in mice. These findings show that a previously unknown epithelial GABAergic system has an essential role in asthma.

  1. Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
  2. Immune Regulation of Allergy Group, Departments of Medical Microbiology and Immunology, University of Manitoba, 730 William Avenue, Winnipeg, Mannitoba R3E 0W3, Canada.
  3. Department of Surgery, University of Toronto, 100 College Street, Toronto, Ontario M5G 1L5, Canada.
  4. Department of Physiology, University of Toronto, 1 King's College Circle, Medical Science Building, Toronto, Ontario M5S 1A8, Canada.
  5. Department of Medicine, Michael G. DeGroot School of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
  6. Institute of Physiology, Medical School of Shandong University, 44 Wenhuaxilu, Jinan, Shandong 250012, China.
  7. Department of Anesthesia, University of Toronto, FitzGerald Building, 150 College Street, Toronto, Ontario M5S 3E2, Canada.

Correspondence to: Wei-Yang Lu1,4,7 e-mail: wlu@sten.sunnybrook.utoronto.ca

Correspondence to: Xi Yang2 e-mail: yangxi@cc.umanitoba.ca


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