title: Recognition of Streptococcus pneumoniae and muramyl dipeptide by NOD2 results in potent induction of MMP-9, which can be controlled by lipopolysaccharide stimulation.
abstract: Matrix metallopeptidase 9 (MMP-9) is a protease involved in the degradation of extracellular matrix collagen. Evidence suggests that MMP-9 is involved in pathogenesis during Streptococcus pneumoniae infection. However, not much is known about the induction of MMP-9 and the regulatory processes involved. We show here that the Gram-positive bacteria used in this study induced large amounts of MMP-9, in contrast to the Gram-negative bacteria that were used. An important pathogen-associated molecular pattern (PAMP) for Gram-positive bacteria is muramyl dipeptide (MDP). MDP is a very potent inducer of MMP-9 and showed a dose-dependent MMP-9 induction. Experiments using peripheral blood mononuclear cells (PBMCs) from Crohn's disease patients with nonfunctional NOD2 showed that MMP-9 induction by Streptococcus pneumoniae and MDP is NOD2 dependent. Increasing amounts of lipopolysaccharide (LPS), an important PAMP for Gram-negative bacteria, resulted in decreasing amounts of MMP-9. Moreover, the induction of MMP-9 by MDP could be counteracted by simultaneously adding LPS. The inhibition of MMP-9 expression by LPS was found to be regulated posttranscriptionally, independently of tissue inhibitor of metalloproteinase 1 (TIMP-1), an endogenous inhibitor of MMP-9. Collectively, these data show that Streptococcus pneumoniae is able to induce large amounts of MMP-9. These high MMP-9 levels are potentially involved in Streptococcus pneumoniae pathogenesis.
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marloes
authors.initials: M
authors.lastname: Vissers
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Hartman
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Groh
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: de Jong
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Center, Nijmegen, The Netherlands Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Gerben.Ferwerda@radboudumc.nl.
authors.forename: Gerben
authors.initials: G
authors.lastname: Ferwerda
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000378:metabolism*; D002478:Cells, Cultured; D003424:Crohn Disease / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9