Maraviroc reduces cytokine expression and secretion in human adipose cells without altering adipogenic differentiation

Díaz-Delfín, Julieta; Domingo, Peré; Giralt, Marta; Villarroya, Francesc

doi:10.1016/j.cyto.2012.12.013

Cited by 25 publications

(17 citation statements)

References 44 publications

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“…Maraviroc concentrations of 0.1-4 μM lowers lipopolysaccharide-induced inflammation in adipocytes, decreasing mRNA and secretion of MCP-1, IL-8, and IL-6 [46]. Maraviroc treatment improves progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome [47] and improves lipid profiles in HIV patients with dyslipidemia [48].…”

Section: Discussionmentioning

confidence: 99%

HIV-1 induces cytoskeletal alterations and Rac1 activation during monocyte-blood–brain barrier interactions: modulatory role of CCR5

Woollard

Singh

et al. 2014

Retrovirology

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BackgroundMost HIV strains that enter the brain are macrophage-tropic and use the CCR5 receptor to bind and infect target cells. Because the cytoskeleton is a network of protein filaments involved in cellular movement and migration, we investigated whether CCR5 and the cytoskeleton are involved in endothelial-mononuclear phagocytes interactions, adhesion, and HIV-1 infection.ResultsUsing a cytoskeleton phospho-antibody microarray, we showed that after co-culture with human brain microvascular endothelial cells (HBMEC), HIV-1 infected monocytes increased expression and activation of cytoskeleton-associated proteins, including Rac1/cdc42 and cortactin, compared to non-infected monocytes co-cultured with HBMEC. Analysis of brain tissues from HIV-1-infected patients validated these findings, and showed transcriptional upregulation of Rac1 and cortactin, as well as increased activation of Rac1 in brain tissues of HIV-1-infected humans, compared to seronegative individuals and subjects with HIV-1-encephalitis. Confocal imaging showed that brain cells expressing phosphorylated Rac1 were mostly macrophages and blood vessels. CCR5 antagonists TAK-799 and maraviroc prevented HIV-induced upregulation and phosphorylation of cytoskeleton-associated proteins, prevented HIV-1 infection of macrophages, and diminished viral-induced adhesion of monocytes to HBMEC. Ingenuity pathway analysis suggests that during monocyte-endothelial interactions, HIV-1 alters protein expression and phosphorylation associated with integrin signaling, cellular morphology and cell movement, cellular assembly and organization, and post-translational modifications in monocytes. CCR5 antagonists prevented these HIV-1-induced alterations.ConclusionsHIV-1 activates cytoskeletal proteins during monocyte-endothelial interactions and increase transcription and activation of Rac1 in brain tissues. In addition to preventing macrophage infection, CCR5 antagonists could diminish viral-induced alteration and phosphorylation of cytoskeletal proteins, monocyte adhesion to the brain endothelium and viral entry into the central nervous system.

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Section: Discussionmentioning

confidence: 99%

HIV-1 induces cytoskeletal alterations and Rac1 activation during monocyte-blood–brain barrier interactions: modulatory role of CCR5

Woollard

Singh

et al. 2014

Retrovirology

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“…Diaz-Delfin et al studied the effects of Maroviroc during and after the differentiation of human adipocytes in culture, and they concluded that Maraviroc did not alter adipocyte differentiation, but showed anti-inflammatory properties, which suggested that Maraviroc could be beneficial by minimizing adverse effects on adipose tissue development, metabolism, and inflammation [50]. …”

Section: Clinical Studiesmentioning

confidence: 99%

Chemokine Receptor CCR5 Antagonist Maraviroc: Medicinal Chemistry and Clinical Applications

Xu¹,

Guo²,

Wu³

2014

CTMC

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The human immunodeficiency virus (HIV) causes acquired immumodeficiency syndrome (AIDS), one of the worst global pandemic. The virus infects human CD4 T cells and macrophages, and causes CD4 depletion. HIV enters target cells through the binding of the viral envelope glycoprotein to CD4 and the chemokine coreceptor, CXCR4 or CCR5. In particular, the CCR5-utilizing viruses predominate in the blood during the disease course. CCR5 is expressed on the surface of various immune cells including macrophages, monocytes, microglia, dendric cells, and active memory CD4 T cells. In the human population, the CCR5 genomic mutation, CCR5Δ32, is associated with relative resistance to HIV. These findings paved the way for the discovery and development of CCR5 inhibitors to block HIV transmission and replication. Maraviroc, discovered as a CCR5 antagonist, is the only CCR5 inhibitor that has been approved by both US FDA and the European Medicines Agency (EMA) for treating HIV/AIDS patients. In this review, we summarize the medicinal chemistry and clinical studies of Maraviroc.

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“…24 Contrarily maraviroc, a chemokine receptor CCR5 antagonist, does not alter adipocyte differentiation and seems to have anti-inflammatory properties exerted by inhibition of the expression and release of pro-inflammatory cytokines. 25 Coinfections and pro-inflammatory pattern HIV itself, especially before the start of HAART, herpesviridae, in particular cytomegalovirus (CMV), and hepatitis viruses cause a prolonged stimulus to the immune system, reducing in particular the capability of proliferation of the T cells and depleting T-cells receptor (TCR) repertoire. 7,8,26 CMV causes a lifelong infection able to produce continuous antigenic stimulation thanks to most of viral proteins (751 unique CMV proteins) in infected cells.…”

Section: Immunology Of Aging In Hiv-infected Patientsmentioning

confidence: 99%

Immunosenescence and hurdles in the clinical management of older HIV-patients

2017

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People living with HIV (PLWH) who are treated with effective highly active antiretroviral therapy (HAART) have a similar life expectancy to the general population. Moreover, an increasing proportion of new HIV diagnoses are made in people older than 50 y. The number of older HIVinfected patients is thus constantly growing and it is expected that by 2030 around 70% of PLWH will be more than 50 y old. On the other hand, HIV infection itself is responsible for accelerated immunosenescence, a progressive decline of immune system function in both the adaptive and the innate arm, which impairs the ability of an individual to respond to infections and to give rise to long-term immunity; furthermore, older patients tend to have a worse immunological response to HAART.In this review we focus on the pathogenesis of HIV-induced immunosenescence and on the clinical management of older HIV-infected patients.

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Maraviroc reduces cytokine expression and secretion in human adipose cells without altering adipogenic differentiation

Cited by 25 publications

References 44 publications

HIV-1 induces cytoskeletal alterations and Rac1 activation during monocyte-blood–brain barrier interactions: modulatory role of CCR5

HIV-1 induces cytoskeletal alterations and Rac1 activation during monocyte-blood–brain barrier interactions: modulatory role of CCR5

Chemokine Receptor CCR5 Antagonist Maraviroc: Medicinal Chemistry and Clinical Applications

Immunosenescence and hurdles in the clinical management of older HIV-patients

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