title: Role of matrix metalloproteinases 2 and 9 in ex vivo Trypanosoma cruzi infection of human placental chorionic villi.
abstract: BACKGROUND
  Chagas' disease is caused by the haemophlagelated protozoan Trypanosoma cruzi (T. cruzi). During congenital transmission the parasite breaks down the placental barrier. In the present study we analyzed the participation of matrix metalloproteases (MMPs) in the extracellular matrix (ECM) remodeling during T. cruzi ex vivo infection of human placental chorionic villi explants.
  
  
  METHODS
  Chorionic villi from healthy woman placentas were incubated in the presence or absence of 10⁵ or 10⁶ T. cruzi trypomastigotes (Y strain) with or without the MMPs inhibitor doxycycline. Effective infection was tested measuring parasite DNA by real time PCR (qPCR). MMP-2 and MMP-9 expression were determined by western blotting and immunohistochemistry and their activities were measured by zymography. The effect of MMPs on ECM structure was analyzed histochemically.
  
  
  RESULTS
  T. cruzi induces the expression and activity of MMP-2 and MMP-9 in chorionic villi. Inhibition of the MMPs prevents the tissue damage induced by T. cruzi and partially decreases the ex vivo infection of the chorionic villi.
  
  
  CONCLUSIONS
  MMPs are partially responsible for the ECM changes observed in human chorionic villi during T. cruzi infection and participate in tissue invasion. On the other hand, MMPs may be part of a local placental antiparasitic mechanism.
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Region Metropolitana, Santiago de Chile 8380453, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Castillo
authors.forename: R
authors.initials: R
authors.lastname: López-Muñoz
authors.forename: J
authors.initials: J
authors.lastname: Duaso
authors.forename: N
authors.initials: N
authors.lastname: Galanti
authors.forename: F
authors.initials: F
authors.lastname: Jaña
authors.forename: J
authors.initials: J
authors.lastname: Ferreira
authors.forename: G
authors.initials: G
authors.lastname: Cabrera
authors.forename: J D
authors.initials: JD
authors.lastname: Maya
authors.forename: U
authors.initials: U
authors.lastname: Kemmerling
mesh_terms: D015153:Blotting, Western; D014355:Chagas Disease / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control / Q000635:transmission; D002824:Chorionic Villi / Q000201:enzymology* / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D016054:DNA, Protozoan / Q000378:metabolism; D060467:Disease Resistance; D004318:Doxycycline / Q000494:pharmacology; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy; D011480:Protease Inhibitors / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects; D046509:Tissue Culture Techniques; D014344:Trypanocidal Agents / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity
chemical_list: D016054:DNA, Protozoan; D016326:Extracellular Matrix Proteins; D011480:Protease Inhibitors; D014344:Trypanocidal Agents; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline