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Effects of Plasmodium falciparum-infected erythrocytes on matrix metalloproteinase-9 regulation in human microvascular endothelial cells.
MedLine Citation:
PMID:  23375032     Owner:  NLM     Status:  In-Data-Review    
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.
Sarah D'Alessandro; Nicoletta Basilico; Mauro Prato
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Asian Pacific journal of tropical medicine     Volume:  6     ISSN:  1995-7645     ISO Abbreviation:  Asian Pac J Trop Med     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101533720     Medline TA:  Asian Pac J Trop Med     Country:  Singapore    
Other Details:
Languages:  eng     Pagination:  195-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
Dipartimento di Sanità Pubblica-Microbiologia-Virologia, Università di Milano, Milano, Italy.
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