Extracellular matrix-remodeling metalloproteinases and infection of the central nervous system with retrovirus human T-lymphotropic virus type I (HTLV-I).
Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are involved in physiological processes and contribute to the phenotype of several pathological conditions associated with uncontrolled tissue degradation. In the central nervous system (CNS), MMPs are thought to play a role in cell migration and synaptic plasticity. We have investigated the expression, regulation and possible role of MMPs and TIMPs during infection of glial cells with human T-lymphotropic virus type I (HTLV-I), the causative agent of a progressive chronic myelopathy, TSP/HAM. The major alteration consists in a high increase in MMP-9 secretion and TIMP-2 mRNA expression. Cytokines TNF alpha and IL1 alpha, induced in glial cells during HTLV-I infection, promote the upregulation of MMP-9. In addition, cerebrospinal fluid from TSP/HAM patients contain high MMP-9 level. The exact role of dysregulated MMPs/TIMPs in the pathogenesis of TSP/HAM is not known; however, functions of these proteases in physiological processes should provide valuable clues. MMPs can affect the blood-brain barrier and the intercellular connectivity by degrading the extracellular matrix of endothelial and neural cells. They can be involved in autoimmunity by generating preformed specific peptides from myelin components. Finally, they can direct and prolong TNF activity in the CNS by converting its inactive precursor into active molecules.
Giraudon
P
P
INSERM, U433-Faculté de Médecine Alexis Carrel, Lyon, France.
Buart
S
S
Bernard
A
A
Thomasset
N
N
Belin
M F
MF
D002490:Central Nervous System / Q000201:enzymology* / Q000821:virology; D006800:Deltaretrovirus Infections / Q000201:enzymology*; D005109:Extracellular Matrix / Q000201:enzymology* / Q000821:virology; D015368:Human T-lymphotropic virus 1; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*
D008666:Metalloendopeptidases