Pseudomonas aeruginosa pyocyanin causes airway goblet cell hyperplasia and metaplasia and mucus hypersecretion by inactivating the transcriptional factor FoxA2

Yonghua Hao, Zhizhou Kuang, Brent E. Walling, Shikha Bhatia, Mayandi Sivaguru, Yin Chen, H. Rex Gaskins, Gee W. Lau

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The redox-active exotoxin pyocyanin (PCN) can be recovered in 100μM concentrations in the sputa of bronchiectasis patients chronically infected with Pseudomonas aeruginosa (PA). However, the importance of PCN within bronchiectatic airways colonized by PA remains unrecognized. Recently, we have shown that PCN is required for chronic PA lung infection in mice, and that chronic instillation of PCN induces goblet cell hyperplasia (GCH), pulmonary fibrosis, emphysema and influx of immune cells in mouse airways. Many of these pathological features are strikingly similar to the mouse airways devoid of functional FoxA2, a transcriptional repressor of GCH and mucus biosynthesis. In this study, we postulate that PCN causes and exacerbates GCH and mucus hypersecretion in bronchiectatic airways chronically infected by PA by inactivating FoxA2. We demonstrate that PCN represses the expression of FoxA2 in mouse airways and in bronchial epithelial cells cultured at an air-liquid interface or conventionally, resulting in GCH, increased MUC5B mucin gene expression and mucus hypersecretion. Immunohistochemical and inhibitor studies indicate that PCN upregulates the expression of Stat6 and EGFR, both of which in turn repress the expression of FoxA2. These studies demonstrate that PCN induces GCH and mucus hypersecretion by inactivating FoxA2.

Original languageEnglish (US)
Pages (from-to)401-415
Number of pages15
JournalCellular Microbiology
Volume14
Issue number3
DOIs
StatePublished - Mar 2012

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Pyocyanine
Goblet Cells
Metaplasia
Mucus
Pseudomonas aeruginosa
Hyperplasia
Exotoxins
Pulmonary Emphysema
Bronchiectasis
Pulmonary Fibrosis
Mucins
Sputum
Oxidation-Reduction
Up-Regulation
Epithelial Cells
Air
Gene Expression

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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Pseudomonas aeruginosa pyocyanin causes airway goblet cell hyperplasia and metaplasia and mucus hypersecretion by inactivating the transcriptional factor FoxA2. / Hao, Yonghua; Kuang, Zhizhou; Walling, Brent E.; Bhatia, Shikha; Sivaguru, Mayandi; Chen, Yin; Gaskins, H. Rex; Lau, Gee W.

In: Cellular Microbiology, Vol. 14, No. 3, 03.2012, p. 401-415.

Research output: Contribution to journalArticle

Hao, Yonghua ; Kuang, Zhizhou ; Walling, Brent E. ; Bhatia, Shikha ; Sivaguru, Mayandi ; Chen, Yin ; Gaskins, H. Rex ; Lau, Gee W. / Pseudomonas aeruginosa pyocyanin causes airway goblet cell hyperplasia and metaplasia and mucus hypersecretion by inactivating the transcriptional factor FoxA2. In: Cellular Microbiology. 2012 ; Vol. 14, No. 3. pp. 401-415.
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