Past Issue

Volume 19, Number 4, Jan-Mar(Winter) 2018, Serial Number: 76 Pages: 559-568

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 PMA- Differentiated THP-1 Cells

Faezeh Maghsood, M.Sc, 1, Abbas Mirshafiey, Ph.D, 1, Mohadese M. Farahani, M.Sc, 1, Mohammad Hossein Modarressi, M.D., Ph.D., 2, Parvaneh Jafari, Ph.D., 3, Elahe Motevaseli, M.D., Ph.D.4, 5, *,
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Department of Microbiology, Science Faculty, Islamic Azad University, Arak Branch, Arak, Iran
Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran
*Corresponding Address: P.O. BOX: 1417743373 Department of Molecular Medicine School of Advanced Technologies in Medicine Tehran University of Medical Sciences Tehran Iran



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 (RT- PCR). 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.


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.


Our results indicate that CFS from L. acidophilus and LGG possess anti-inflammatory properties and can modulate the inflammatory response.