Evidence on the involvement of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in complicated malaria has been emerging recently. Here the effects of malarial pigment haemozoin (HZ) on MMP-9/TIMP-1 balance in human monocytes were studied. HZ enhanced MMP-9 and TIMP-1 mRNA expression and protein release, as well as net total gelatinolytic activity and cell invasiveness. HZ-dependent MMP-9/TIMP-1 enhancement was abrogated by anti-TNFalpha, -IL-1beta, -MIP-1alpha antibodies and mimicked by recombinant cytokines. Lipid-free HZ did not reproduce HZ effects; HZ lipoperoxidation derivative 15-HETE did. NF-kappaB inhibitors abrogated HZ effects. Taken altogether, the present data suggest that in human monocytes the lipid moiety of HZ promotes NF-kappaB-dependent and inflammation-mediated increase of MMP-9/TIMP-1 expression and release. HZ enhances net gelatinolytic activity and cell invasion ability, suggesting that TIMP-1 enhancement is not sufficient to counterbalance MMP-9 increase. Nevertheless, TIMP-1 anti-apoptotic and growth-inhibitory properties could explain some features of HZ-fed monocytes, including prolonged survival, lack of maturation to dendritic cells and erythropoiesis inhibition.
Malarial pigment alters MMP-9/TIMP-1 balance in human monocytes
PRATO, Mauro;VALENTE, Elena;POLIMENI, Manuela;ULLIERS, Daniela;KHADJAVI, AMINA;MANDILI, GIORGIA;GIRIBALDI, Giuliana
2011-01-01
Abstract
Evidence on the involvement of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in complicated malaria has been emerging recently. Here the effects of malarial pigment haemozoin (HZ) on MMP-9/TIMP-1 balance in human monocytes were studied. HZ enhanced MMP-9 and TIMP-1 mRNA expression and protein release, as well as net total gelatinolytic activity and cell invasiveness. HZ-dependent MMP-9/TIMP-1 enhancement was abrogated by anti-TNFalpha, -IL-1beta, -MIP-1alpha antibodies and mimicked by recombinant cytokines. Lipid-free HZ did not reproduce HZ effects; HZ lipoperoxidation derivative 15-HETE did. NF-kappaB inhibitors abrogated HZ effects. Taken altogether, the present data suggest that in human monocytes the lipid moiety of HZ promotes NF-kappaB-dependent and inflammation-mediated increase of MMP-9/TIMP-1 expression and release. HZ enhances net gelatinolytic activity and cell invasion ability, suggesting that TIMP-1 enhancement is not sufficient to counterbalance MMP-9 increase. Nevertheless, TIMP-1 anti-apoptotic and growth-inhibitory properties could explain some features of HZ-fed monocytes, including prolonged survival, lack of maturation to dendritic cells and erythropoiesis inhibition.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
