Nebulized Menthol Impairs Mucociliary Clearance via TRPM8 and MUC5AC/MUC5B in Primary Airway Epithelial Cells

Nathalie Baumlin1, Neerupma Silswal1, John S Dennis1

  • 1Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Insights

Inhaled menthol in e-cigarettes significantly impairs airway clearance mechanisms, reducing ciliary beat frequency and increasing mucus. This suggests menthol poses risks to respiratory health at typical e-cigarette concentrations.

Area of Science:

  • Respiratory Physiology
  • Toxicology
  • Cell Biology

Background:

  • Menthol is a popular flavoring in e-cigarettes, approved by the FDA for some products.
  • The safety of high menthol concentrations inhaled from e-cigarettes is not well understood.

Purpose of the Study:

  • To investigate the effects of menthol on mucociliary clearance (MCC) in airway epithelial cells.
  • To determine the impact of menthol on ciliary function, mucus production, and inflammation.

Main Methods:

  • Utilized air-liquid interface (ALI) cultures of primary human airway epithelial cells.
  • Applied menthol via basolateral treatment and nebulization.
  • Measured ciliary beat frequency (CBF), airway surface liquid (ASL) volume, mucin production, and inflammatory cytokine expression (IL1B, TNFA).
  • Investigated the role of the TRPM8 channel.

Main Results:

  • Menthol significantly decreased CBF and ASL volume.
  • Nebulized menthol reduced mucociliary transport by increasing mucus concentration.
  • Menthol increased MUC5AC expression and inflammatory cytokine mRNA levels (IL1B, TNFA).
  • Menthol activated TRPM8, and TRPM8 antagonism blocked menthol's adverse effects.

Conclusions:

  • Menthol, at concentrations relevant to e-cigarette use, impairs crucial airway clearance functions.
  • Menthol exposure can lead to increased mucus production and airway inflammation.
  • The TRPM8 channel mediates menthol's detrimental effects on airway epithelium.

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