Effect of microbial siderophores on matrix metalloproteinase-2 activity

Matrix metalloproteinases (MMPs) are capable of cleaving almost all macromo lecules of the extracellular connective tissue matrix and are thought to pl ay a major role in tissue destructive inflammatory diseases such as periodo ntitis. The aim of this study was to determine the effects of siderophores, which are iron-chelating molecules produced by a variety of microorganisms , on the activity of MMP-2. Heat-denatured type I collagen (gelatin) was in cubated with p-aminophenylmercuric acetate-activated MMP-2 and siderophores . Degradation of gelatin was monitored by SDS-PAGE and Coomassie blue stain ing. Ferrichrome, rhodotorulic acid, desferoxamine mesylate and 2,3-dihydro xybenzoic acid were found to inhibit the MMP-2 activity whereas beta-phenyl pyruvic acid had no effect. The inhibition could be reversed by adding an e xcess calcium chloride or ferric chloride to the assay mixtures, Our study suggests that microbial siderophores may represent new-potential therapeuti c molecules for the treatment of destructive inflammatory diseases involvin g excess MMP-2 activity, such as periodontitis.