Alternaria induces airway epithelial cytokine expression independent of protease-activated receptor

Michael Daines, Lingxiang Zhu, Rhea Pereira, Xu Zhou, Cheryl Bondy, Barry M. Pryor, Jin Zhou, Yin Chen

Research output: Contribution to journalArticle

Abstract

Background and objective: A novel fungal allergen, Alternaria (Alt), has been previously shown to associate with the pathogenesis of allergic rhinitis and bronchial asthma, particularly in arid and semi-arid regions. Airway epithelial cells are among the first to encounter Alt, and epithelial cytokine production and subsequent airway inflammation are early events in the response to Alt exposure. However, the underlying mechanism is unclear. As protease-activated receptor 2 (PAR2) has been implicated in most of the Alt-induced biological events, we investigated the regulation of airway inflammation and epithelial cytokine expression by PAR2. Methods: Wild-type (WT) and Par2 knockout (Par2-KO) mice were used to evaluate the in vivo role of PAR2. Primary human and mouse airway epithelial cells were used to examine the mechanistic basis of epithelial cytokine regulation in vitro. Results: Surprisingly, Par2 deficiency had no negative impact on the change of lung function, inflammation and cytokine production in the mouse model of Alt-induced asthma. Alt-induced cytokine production in murine airway epithelial cells from Par2-KO mice was not significantly different from the WT cells. Consistently, PAR2 knockdown in human cells also had no effect on cytokine expression. In contrast, the cytokine expressions induced by synthetic PAR2 agonist or other asthma-related allergens (e.g. cockroach extracts) were indeed mediated via a PAR2-dependent mechanism. Finally, we found that EGFR pathway was responsible for Alt-induced epithelial cytokine expression. Conclusion: The activation of EGFR, but not PAR2, was likely to drive the airway inflammation and epithelial cytokine production induced by Alt.

Original languageEnglish (US)
JournalRespirology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Proteinase-Activated Receptors
Alternaria
PAR-2 Receptor
Cytokines
Asthma
Epithelial Cells
Inflammation
Knockout Mice
Allergens
Cockroaches
Pneumonia

Keywords

  • airway
  • Alternaria
  • cytokine
  • EGFR
  • epithelium

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Alternaria induces airway epithelial cytokine expression independent of protease-activated receptor. / Daines, Michael; Zhu, Lingxiang; Pereira, Rhea; Zhou, Xu; Bondy, Cheryl; Pryor, Barry M.; Zhou, Jin; Chen, Yin.

In: Respirology, 01.01.2019.

Research output: Contribution to journalArticle

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