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Doxycycline attenuates acrolein-induced mucin production, in part by inhibiting MMP-9

Shuang Ren1, Ling-Li Guo, Jie Yang

  • 1Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, China.

European Journal of Pharmacology
|November 2, 2010
PubMed

Insights

Doxycycline, an MMP inhibitor, reduced mucus production in rats exposed to acrolein. This suggests doxycycline may prevent smoking-induced mucus hypersecretion by inhibiting MMP-9 and MUC5AC expression.

Area of Science:

  • Respiratory Medicine
  • Pharmacology
  • Biochemistry

Background:

  • Matrix metalloproteinases (MMPs), particularly MMP-9, are implicated in regulating airway mucin expression.
  • Epidermal growth factor (EGF) receptor signaling may mediate acrolein-induced mucin production.

Purpose of the Study:

  • To investigate the effect of doxycycline, an MMP inhibitor, on mucus production and MUC5AC synthesis in acrolein-exposed rats.
  • To determine if doxycycline attenuates acrolein-induced MMP-9 and MUC5AC expression.

Main Methods:

  • Sprague-Dawley rats were exposed to acrolein aerosol for 12 days.
  • Doxycycline (20mg/kg) was administered daily via gavage starting before acrolein exposure.
  • Tracheal mucin glycoprotein production, MMP-9, and MUC5AC gene expression were measured.

Main Results:

  • Acrolein exposure increased MMP-9 mRNA and protein levels, alongside MUC5AC mRNA expression in the airway epithelium.
  • Doxycycline treatment significantly inhibited these acrolein-induced increases in MMP-9 and MUC5AC.
  • Doxycycline attenuated mucus production in the tracheal epithelium.

Conclusions:

  • Doxycycline mitigates acrolein-induced mucin synthesis, partly by inhibiting MMP-9 expression.
  • Doxycycline demonstrates potential as a prophylactic treatment for smoking-induced mucus hypersecretion.

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