Antiretroviral therapy inhibits matrix metalloproteinase-9 from blood mononuclear cells of HIV-infected patients

Abstract

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