title: Effects of Plasmodium falciparum-infected erythrocytes on matrix metalloproteinase-9 regulation in human microvascular endothelial cells.
abstract: OBJECTIVE
  To investigate the regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human microvascular endothelium (HMEC-1) exposed to erythrocytes infected by different strains of Plasmodium falciparum (P. falciparum).
  
  
  METHODS
  HMEC-1 cells were co-incubated for 72 h with erythrocytes infected by late stage trophozoite of D10 (chloroquine-sensitive) or W2 (chloroquine-resistant) P. falciparum strains. Cell supernatants were then collected and the levels of pro- or active gelatinases MMP-9 and MMP-2 were evaluated by gelatin zymography and densitometry. The release of pro-MMP-9, MMP-3, MMP-1 and TIMP-1 proteins was analyzed by western blotting and densitometry.
  
  
  RESULTS
  Infected erythrocytes induced de novo proMMP-9 and MMP-9 release. Neither basal levels of proMMP-2 were altered, nor active MMP-2 was found. MMP-3 and MMP-1 secretion was significantly enhanced, whereas basal TIMP-1 was unaffected. All effects were similar for both strains.
  
  
  CONCLUSIONS
  P. falciparum parasites, either chloroquine-sensitive or -resistant, induce the release of active MMP-9 protein from human microvascular endothelium, by impairing balances between proMMP-9 and its inhibitor, and by enhancing the levels of its activators. This work provides new evidence on MMP involvement in malaria, pointing at MMP-9 as a possible target in adjuvant therapy.
authors: Dipartimento di Sanità Pubblica-Microbiologia-Virologia, Università di Milano, Milano, Italy.
authors: Sarah
authors: S
authors: D'Alessandro
authors: Nicoletta
authors: N
authors: Basilico
authors: Mauro
authors: M
authors: Prato
mesh_terms: D015153:Blotting, Western; D003720:Densitometry; D042783:Endothelial Cells / Q000378:metabolism* / Q000469:parasitology; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism* / Q000472:pathogenicity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1