In vitro downregulation of matrix metalloproteinase-9 in rat glial cells by CCR5 antagonist maraviroc: therapeutic implication for HIV brain infection.

<h4>Background</h4>Matrix metalloproteinases (MMPs) released by glial cells are important mediators of neuroinflammation and neurologic damage in HIV infection. The use of antiretroviral drugs able to combat the detrimental effect of chronic inflammation and target the exaggerated MMP ac...

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Autores principales:	Pasqua Gramegna, Tiziana Latronico, Maria Teresa Branà, Gaetano Di Bari, Fabio Mengoni, Valeria Belvisi, Maria T Mascellino, Miriam Lichtner, Vincenzo Vullo, Claudio M Mastroianni, Grazia M Liuzzi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6deeda565a33498bb67337185076b4f1
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spelling	oai:doaj.org-article:6deeda565a33498bb67337185076b4f12021-11-18T07:32:44ZIn vitro downregulation of matrix metalloproteinase-9 in rat glial cells by CCR5 antagonist maraviroc: therapeutic implication for HIV brain infection.1932-620310.1371/journal.pone.0028499https://doaj.org/article/6deeda565a33498bb67337185076b4f12011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174822/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Matrix metalloproteinases (MMPs) released by glial cells are important mediators of neuroinflammation and neurologic damage in HIV infection. The use of antiretroviral drugs able to combat the detrimental effect of chronic inflammation and target the exaggerated MMP activity might represent an attractive therapeutic challenge. Recent studies suggest that CCR5 antagonist maraviroc (MVC) exerts immunomodulant and anti-inflammatory activity beyond its anti-HIV properties. We investigated the in vitro effect of MVC on the activity of MMPs in astrocyte and microglia cultures.<h4>Methodology/principal findings</h4>Primary cultures of rat astrocytes and microglia were activated by exposure to phorbol myristate acetate (PMA) or lypopolysaccharide (LPS) and treated in vitro with MVC. Culture supernatants were subjected to gelatin zymography and quantitative determination of MMP-9 and MMP-2 was done by computerized scanning densitometry. MMP-9 levels were significantly elevated in culture supernatants from both LPS- and PMA-activated astrocytes and microglia in comparison to controls. The treatment with MVC significantly inhibited in a dose-dependent manner the levels and expression of MMP-9 in PMA-activated astrocytes (p<0,05) and, to a lesser extent, in PMA-activated microglia. By contrast, levels of MMP-2 did not significantly change, although a tendency to decrease was seen in PMA-activated astrocytes after treatment with MVC. The inhibition of levels and expression of MMP-9 in PMA-activated glial cells did not depend on cytotoxic effects of MVC. No inhibition of MMP-9 and MMP-2 were found in both LPS-activated astrocytes and microglia.<h4>Conclusions</h4>The present in vitro study suggests that CCR5 antagonist compounds, through their ability to inhibit MMP-9 expression and levels, might have a great potential for the treatment of HIV-associated neurologic damage.Pasqua GramegnaTiziana LatronicoMaria Teresa BranàGaetano Di BariFabio MengoniValeria BelvisiMaria T MascellinoMiriam LichtnerVincenzo VulloClaudio M MastroianniGrazia M LiuzziPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e28499 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pasqua Gramegna Tiziana Latronico Maria Teresa Branà Gaetano Di Bari Fabio Mengoni Valeria Belvisi Maria T Mascellino Miriam Lichtner Vincenzo Vullo Claudio M Mastroianni Grazia M Liuzzi In vitro downregulation of matrix metalloproteinase-9 in rat glial cells by CCR5 antagonist maraviroc: therapeutic implication for HIV brain infection.
description	<h4>Background</h4>Matrix metalloproteinases (MMPs) released by glial cells are important mediators of neuroinflammation and neurologic damage in HIV infection. The use of antiretroviral drugs able to combat the detrimental effect of chronic inflammation and target the exaggerated MMP activity might represent an attractive therapeutic challenge. Recent studies suggest that CCR5 antagonist maraviroc (MVC) exerts immunomodulant and anti-inflammatory activity beyond its anti-HIV properties. We investigated the in vitro effect of MVC on the activity of MMPs in astrocyte and microglia cultures.<h4>Methodology/principal findings</h4>Primary cultures of rat astrocytes and microglia were activated by exposure to phorbol myristate acetate (PMA) or lypopolysaccharide (LPS) and treated in vitro with MVC. Culture supernatants were subjected to gelatin zymography and quantitative determination of MMP-9 and MMP-2 was done by computerized scanning densitometry. MMP-9 levels were significantly elevated in culture supernatants from both LPS- and PMA-activated astrocytes and microglia in comparison to controls. The treatment with MVC significantly inhibited in a dose-dependent manner the levels and expression of MMP-9 in PMA-activated astrocytes (p<0,05) and, to a lesser extent, in PMA-activated microglia. By contrast, levels of MMP-2 did not significantly change, although a tendency to decrease was seen in PMA-activated astrocytes after treatment with MVC. The inhibition of levels and expression of MMP-9 in PMA-activated glial cells did not depend on cytotoxic effects of MVC. No inhibition of MMP-9 and MMP-2 were found in both LPS-activated astrocytes and microglia.<h4>Conclusions</h4>The present in vitro study suggests that CCR5 antagonist compounds, through their ability to inhibit MMP-9 expression and levels, might have a great potential for the treatment of HIV-associated neurologic damage.
format	article
author	Pasqua Gramegna Tiziana Latronico Maria Teresa Branà Gaetano Di Bari Fabio Mengoni Valeria Belvisi Maria T Mascellino Miriam Lichtner Vincenzo Vullo Claudio M Mastroianni Grazia M Liuzzi
author_facet	Pasqua Gramegna Tiziana Latronico Maria Teresa Branà Gaetano Di Bari Fabio Mengoni Valeria Belvisi Maria T Mascellino Miriam Lichtner Vincenzo Vullo Claudio M Mastroianni Grazia M Liuzzi
author_sort	Pasqua Gramegna
title	In vitro downregulation of matrix metalloproteinase-9 in rat glial cells by CCR5 antagonist maraviroc: therapeutic implication for HIV brain infection.
title_short	In vitro downregulation of matrix metalloproteinase-9 in rat glial cells by CCR5 antagonist maraviroc: therapeutic implication for HIV brain infection.
title_full	In vitro downregulation of matrix metalloproteinase-9 in rat glial cells by CCR5 antagonist maraviroc: therapeutic implication for HIV brain infection.
title_fullStr	In vitro downregulation of matrix metalloproteinase-9 in rat glial cells by CCR5 antagonist maraviroc: therapeutic implication for HIV brain infection.
title_full_unstemmed	In vitro downregulation of matrix metalloproteinase-9 in rat glial cells by CCR5 antagonist maraviroc: therapeutic implication for HIV brain infection.
title_sort	in vitro downregulation of matrix metalloproteinase-9 in rat glial cells by ccr5 antagonist maraviroc: therapeutic implication for hiv brain infection.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/6deeda565a33498bb67337185076b4f1
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In vitro downregulation of matrix metalloproteinase-9 in rat glial cells by CCR5 antagonist maraviroc: therapeutic implication for HIV brain infection.

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