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

Matrix metalloproteinases (MMPs) especially MMP-9 have been found to increase the expression of epidermal growth factor (EGF) receptor a possible regulator of acrolein-induced mum expression in the airway epithelium The aim of this study was to investigate whether doxycycline a tetracycline antibiotic that inhibits MMPs attenuates mucus production and synthesis of mum MUC5AC in acrolein-exposed rats Sprague-Dawley rats were exposed to acrolein aerosol [3 0 parts/million (ppm) 6 h/day 12 days] and they received 20 mg/kg doxycycline daily by gavage beginning two days before exposure to acrolein until the end of the experiment The production of mucin glycoproteins and expression of the MMP-9 and MUC5AC genes were measured in rat trachea The increase in levels of MMP 9 mRNA and protein in airway epithelium after acrolein exposure was accompanied by an increase in MUC5AC mRNA expression Doxycycline significantly prevented these increases in acrolein induced expression of MMP 9 and MUC5AC and attenuated mucus production in tracheal epithelium These results indicate that doxycycline attenuated acrolein induced mucin synthesis in part by inhibiting expression of MMP-9 Thus doxycycline may have a prophylactic effect in the treatment of smoking-induced mucus hypersecretion Crown Copyright (C) 2010 Published by Elsevier B V All rights reserved