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
Effects of Plasmodium falciparum-infected erythrocytes on matrix metalloproteinase-9 regulation in human microvascular endothelial cells / S. D'Alessandro, N. Basilico, M. Prato. - In: ASIAN PACIFIC JOURNAL OF TROPICAL MEDICINE. - ISSN 1995-7645. - 6:3(2013 Mar), pp. 195-199. [10.1016/S1995-7645(13)60022-X]
Effects of Plasmodium falciparum-infected erythrocytes on matrix metalloproteinase-9 regulation in human microvascular endothelial cells
S. D'AlessandroPrimo
;N. BasilicoSecondo
;
2013
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 therapyPubblicazioni consigliate
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