title: Macrophage inflammatory protein-1alpha mediates matrix metalloproteinase-9 enhancement in human adherent monocytes fed with malarial pigment.
abstract: OBJECTIVE
  To investigate the role of macrophage inflammatory protein-1alpha (MIP-1alpha) in the detrimental enhancement of matrix metalloproteinase-9 (MMP-9) expression, release and activity induced by phagocytosis of malarial pigment (haemozoin, HZ) in human monocytes.
  
  
  METHODS
  Human adherent monocytes were unfed/fed with native HZ for 2 h. After 24 hours, MIP-1alpha production was evaluated by ELISA in cell supernatants. Alternatively, HZ-unfed/fed monocytes were treated in presence/absence of anti-human MIP-1alpha blocking antibodies or recombinant human MIP-1alpha for 15 h (RNA studies) or 24 h (protein studies); therefore, MMP-9 mRNA expression was evaluated in cell lysates by Real Time RT-PCR, whereas proMMP-9 and active MMP-9 protein release were measured in cell supernatants by Western blotting and gelatin zymography.
  
  
  RESULTS
  Phagocytosis of HZ by human monocytes increased production of MIP-1 alpha, mRNA expression of MMP-9 and protein release of proMMP-9 and active MMP-9. All the HZ-enhancing effects on MMP-9 were abrogated by anti-human MIP-1alpha blocking antibodies and mimicked by recombinant human MIP-1alpha.
  
  
  CONCLUSIONS
  The present work suggests a role for MIP-1alpha in the HZ-dependent enhancement of MMP-9 expression, release and activity observed in human monocytes, highlighting new detrimental effects of HZ-triggered proinflammatory response by phagocytic cells in falciparum malaria.
authors: Dipartimento di Genetica, Biologia e Biochimica, Facoltà di Medicina e Chirurgia, Università degli studi di Torino, Italy.
authors: Giuliana
authors: G
authors: Giribaldi
authors: Elena
authors: E
authors: Valente
authors: Amina
authors: A
authors: Khadjavi
authors: Manuela
authors: M
authors: Polimeni
authors: Mauro
authors: M
authors: Prato
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D015153:Blotting, Western; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006420:Hemeproteins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D054405:Chemokine CCL3; D006420:Hemeproteins; C020753:hemozoin; D020780:Matrix Metalloproteinase 9