dual effects of cell free supernatants from lactobacillus acidophilus and lactobacillus rhamnosus gg in regulation of mmp-9 by up-regulating timp-1 and down-regulating cd147 in pmadifferentiated thp-1 cells

Objective: recent studies have reported dysregulated expression of matrix metalloproteinases (mmps), especially mmp-2, mmp-9, tissue inhibitor of metalloproteinase-1, -2 (timp-1, timp-2), and extracellular matrix metalloproteinase inducer (emmprin/cd147) in activated macrophages of patients with inflammatory diseases. therefore, mmp-2, mmp-9, and their regulators may represent a new target for treatment of inflammatory diseases. probiotics, which are comprised of lactic acid bacteria, have the potential to modulate inflammatory responses. in this experimental study, we investigated the anti-inflammatory effects of cell-free supernatants (cfs) from lactobacillus acidophilus (l. acidophilus) and l. rhamnosus gg (lgg) in phorbol myristate acetate (pma)-differentiated thp-1 cells. materials and methods: in this experimental study, pma-differentiated thp-1 cells were treated with cfs from l. acidophilus, lgg and uninoculated bacterial growth media (as a control). the expression of mmp-2, mmp-9, timp-1, and timp-2 mrnas were determined using real-time quantitative reverse transcription polymerase chain reaction (rtpcr). the levels of cellular surface expression of cd147 were assessed by flow cytometry, and the gelatinolytic activity of mmp-2 and mmp-9 were determined by zymography. results: our results showed that cfs from both l. acidophilus and lgg significantly inhibited the gene expression of mmp-9 (p=0.0011 and p=0.0005, respectively), increased the expression of timp-1 (p<0.0001), decreased the cell surface expression of cd147 (p=0.0307 and p=0.0054, respectively), and inhibited the gelatinolytic activity of mmp-9 (p=0.0003 and p<0.0001, respectively) in pma-differentiated thp-1 cells. although, mmp-2 expression and activity and timp-2 expression remained unchanged. conclusion: our results indicate that cfs from l. acidophilus and lgg possess anti-inflammatory properties and can modulate the inflammatory response.