Suppression of matrix metalloproteinase production from nasal fibroblasts by macrolide antibiotics in vitro.

It is well known that low-dose and long-term administration of macrolide antibiotics favourably modify the clinical status of chronic airway inflammatory diseases. However, the therapeutic mode of action of macrolide antibiotics is not well understood. The present study aimed to examine the influence of macrolide antibiotics, roxithromycin (RXM) and josamycin (JM) on matrix metalloproteinase (MMP) production from nasal polyp fibroblasts (NPF) in vitro. NPF, at a concentration of 2.5 x 10(5) cells x mL(-1), were stimulated with tumour necrosis factor (TNF)-alpha in the presence of various concentrations of RXM or JM for 24 h. MMP-2 and -9 levels in culture supernatants were analysed by ELISA, and MMP mRNA expression was examined by RT-PCR. The influence of RXM on nuclear factor (NF)-kappaB and activator protein (AP)-1 activation was also examined. Addition of RXM (but not JM) at 5.0 and 7.5 microg x mL(-1) significantly suppressed the production of MMP-2 and -9 from NPF induced by TNF-alpha stimulation. RXM also suppressed MMP mRNA expression through the inhibition of NF-kappaB and AP-1 activation. The present results suggest that the suppressive activity of roxithromycin on MMP-2 and -9 production is, in part, responsible for the therapeutic action of macrolides on chronic airway inflammatory diseases.