Antiretroviral therapy inhibits matrix metalloproteinase-9 from blood mononuclear cells of HIV-infected patients.
OBJECTIVE
To investigate whether antiretroviral therapy (ART) influences the release of matrix metalloproteinase (MMP)-9 from peripheral blood mononuclear cells (PBMC) of HIV-infected individuals.


METHODS
Culture supernatants were collected from PBMC isolated from 46 HIV-infected subjects and 19 healthy donors (HD). Among the HIV-infected subjects, 30 were receiving ART therapy, while 16 were naive for any ART treatment.


METHODS
Zymography of culture supernatants was followed by determination of MMP-9 using computered scanning densitometry. MMP-9 net enzymatic activity was determined by the sensitive fluorescent-activated substrate conversion assay (FASC) to complement the zymography data.


RESULTS
MMP-9 was significantly elevated in culture supernatants from PBMC of ART-naive subjects in comparison with HD. In the supernatants from 30 HIV-infected subjects receiving ART therapy, MMP-9 was significantly lower than that in those from ART-naive subjects. Analysis by the reverse transcriptase polymerase chain reaction indicated that MMP-9 expression was increased in ART-naive subjects in comparison with HD but ART induced a decrease of MMP-9 expression to levels comparable with those of HD. FASC used as a functional assay showed conversion of fluorescent gelatine in ART-naive subjects, indicating the presence of active MMP-9. By contrast, in both HD and ART-treated subjects, there was no MMP-9 activity, indicating that MMP-9 was completely blocked by binding to its natural tissue inhibitor TIMP-1.


CONCLUSIONS
The present findings show for the first time that ART can reduce the capacity of PBMC from HIV-infected patients to secrete increased amounts of MMP-9.
Latronico
Tiziana
T
Department of Biochemistry and Molecular Biology, University of Bari, Italy.
Liuzzi
Grazia M
GM
Riccio
Paolo
P
Lichtner
Miriam
M
Mengoni
Fabio
F
D'Agostino
Claudia
C
Vullo
Vincenzo
V
Mastroianni
Claudio M
CM
D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000276:immunology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019562:Viral Load
D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D020780:Matrix Metalloproteinase 9