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. DESIGN: 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.
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. DESIGN: 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-infectedpatients to secrete increased amounts of MMP-9.
Authors: Krystal Colon; Juliana Perez-Laspiur; Raymond Quiles; Yolanda Rodriguez; Valerie Wojna; Scott A Shaffer; John Leszyk; Richard L Skolasky; Loyda M Melendez Journal: Proteomics Clin Appl Date: 2015-11-18 Impact factor: 3.494
Authors: Suyang Li; Ying Wu; Sheila M Keating; Hongyan Du; Christina L Sammet; Cindy Zadikoff; Riti Mahadevia; Leon G Epstein; Ann B Ragin Journal: J Neurovirol Date: 2013-08-27 Impact factor: 2.643
Authors: Milena S Espíndola; Leonardo J G Lima; Luana S Soares; Maira C Cacemiro; Fabiana A Zambuzi; Matheus de Souza Gomes; Laurence R Amaral; Valdes R Bollela; Olindo A Martins-Filho; Fabiani G Frantz Journal: PLoS One Date: 2015-12-18 Impact factor: 3.240