Recombinant gp120 induces IL-10 in resting peripheral blood mononuclear cells; correlation with the induction of other cytokines

Ameglio, F.; Capobianchi, Maria Rosaria; Castilletti, Concetta; Fei, P. Cordiali; Fais, Stefano; Trento, Elisabetta; Dianzani, F.

doi:10.1111/j.1365-2249.1994.tb07018.x

Cited by 51 publications

(10 citation statements)

References 27 publications

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“…21 To our knowledge, this is the first study to find an association between gp120 concentration and cytokine levels in the plasma of HIV-infected individuals. The mechanisms by which gp120 induces cytokines has not been completely defined.…”

Section: 21-23mentioning

confidence: 80%

“…It has been suggested that binding of gp120 to CD4 on T cells, macrophages, and dendritic cells induces a signaling cascade that up-regulates the production of these cytokines. 7,21 Increased production of these cytokines in HIV-infected subjects with detectable levels of gp120 provides evidence that gp120 contributes to the cytokine dysregulation that is common during primary HIV infection.…”

Section: 21-23mentioning

confidence: 99%

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Detection of HIV gp120 in Plasma During Early HIV Infection Is Associated with Increased Proinflammatory and Immunoregulatory Cytokines

Rychert

Strick

Bazner

et al. 2010

AIDS Research and Human Retroviruses

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Events that occur during acute HIV infection likely contribute to the immune dysfunction common in HIVinfected individuals. During this early stage, there is high-level viral replication, loss in CD4 þ T cell number and function, and an up-regulation of proinflammatory and immunoregulatory cytokines. The mechanisms responsible for this are not completely understood. We hypothesize that the HIV envelope glycoprotein, gp120, contributes to immune dysfunction during early HIV infection. Using a cohort of subjects enrolled during acute and early HIV infection, we determined the amount of gp120, TNF-a, IL-6, IL-10, IFN-a, and IFN-g in plasma at baseline and 6 months. At matched time points, we also measured CD4 þ T cell proliferation, T cell activation, and apoptosis. Plasma from 109 subjects was screened for gp120. Thirty-six subjects (33%) had detectable gp120 (0.5-15.6 ng/ml). Subjects with greater than 1 ng/ml of gp120 at baseline had similar levels at all time points tested, even when viral replication was undetectable due to therapy. Subjects with detectable gp120 had higher levels of plasma IL-6, IL-10, and TNF-a. There was no difference in the level of T cell activation, proliferation, or apoptosis in subjects with gp120 compared to those without. We conclude that persistent expression of gp120 occurs in a subset of individuals. Furthermore, the presence of gp120 is associated with higher levels of plasma IL-6, IL-10, and TNF-a, which may contribute to immune dysfunction during early HIV infection.

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Section: 21-23mentioning

confidence: 80%

Section: 21-23mentioning

confidence: 99%

Detection of HIV gp120 in Plasma During Early HIV Infection Is Associated with Increased Proinflammatory and Immunoregulatory Cytokines

Rychert

Strick

Bazner

et al. 2010

AIDS Research and Human Retroviruses

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show abstract

“…Thus, it is essential to determine the viral components responsible for the inflammatory response and to understand the underlying mechanisms and signaling pathways. Several studies have reported the role of HIV-1 proteins, including gp120 [ 18 – 21 ], Tat [ 22 – 25 ], Nef [ 26 – 28 ] and Vpr [ 29 , 30 ] gene products in the immune system dysregulation seen during HIV-1 persistent infection. Some ss-RNA domains expressed by the HIV-1 genome, and HIV-1 gene products act as PAMPs targeting membrane and cytoplasmic PRRs, including TLR2 [ 31 ], TLR3 [ 32 ], TLR4 [ 29 , 33 ], TLR7 [ 34 ], TLR8 [ 35 , 36 ] and RIG-1 [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 Tat Protein Induces Production of Proinflammatory Cytokines by Human Dendritic Cells and Monocytes/Macrophages through Engagement of TLR4-MD2-CD14 Complex and Activation of NF-κB Pathway

et al. 2015

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We recently reported that the human immunodeficiency virus type-1 (HIV-1) Tat protein induced the expression of programmed death ligand-1 (PD-L1) on dendritic cells (DCs) through a TLR4 pathway. However, the underlying mechanisms by which HIV-1 Tat protein induces the abnormal hyper-activation of the immune system seen in HIV-1 infected patients remain to be fully elucidated. In the present study, we report that HIV-1 Tat protein induced the production of significant amounts of the pro-inflammatory IL-6 and IL-8 cytokines by DCs and monocytes from both healthy and HIV-1 infected patients. Such production was abrogated in the presence of anti-TLR4 blocking antibodies or soluble recombinant TLR4-MD2 as a decoy receptor, suggesting TLR4 was recruited by Tat protein. Tat-induced murine IL-6 and CXCL1/KC a functional homologue of human IL-8 was abolished in peritoneal macrophages derived from TLR4 KO but not from Wt mice, confirming the involvement of the TLR4 pathway. Furthermore, the recruitment of TLR4-MD2-CD14 complex by Tat protein was demonstrated by the activation of TLR4 downstream pathways including NF-κB and SOCS-1 and by down-modulation of cell surface TLR4 by endocytosis in dynamin and lipid-raft-dependent manners. Collectively, these findings demonstrate, for the first time, that HIV-1 Tat interacts with TLR4-MD2-CD14 complex and activates the NF-κB pathway, leading to overproduction of IL-6 and IL-8 pro-inflammatory cytokines by myeloid cells from both healthy and HIV-1 infected patients. This study reveals a novel mechanism by which HIV-1, via its early expressed Tat protein, hijacks the TLR4 pathway, hence establishing abnormal hyper-activation of the immune system.

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“…There are many HIV-1 proteins that are capable of inducing the production of several cytokines. These proteins include HIV-1 glycoprotein gp120 that induce the secretion of many pro-inflammatory cytokines including IL-1, IL-6, IL-8, TNF-, and IFN- (Francis and Meltzer 1993;Ameglio, Capobianchi et al 1994;Ankel, Capobianchi et al 1994;Capobianchi, Barresi et al 1997). Interestingly, gp120 is also able to induce the secretion of IL-4 and IL-13 in basophils and IL-10 in mononuclear cells.…”

Section: Hiv and Immunological Disordersmentioning

confidence: 99%

HIV Infection «HIV Tat Protein, a Key Factor in Pathogenesis and Immune System Dysregulation: Implication of IL-10»

Haij¹,

Planès²,

Mzoughi³

et al. 2011

HIV-Host Interactions

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Recombinant gp120 induces IL-10 in resting peripheral blood mononuclear cells; correlation with the induction of other cytokines

Cited by 51 publications

References 27 publications

Detection of HIV gp120 in Plasma During Early HIV Infection Is Associated with Increased Proinflammatory and Immunoregulatory Cytokines

Detection of HIV gp120 in Plasma During Early HIV Infection Is Associated with Increased Proinflammatory and Immunoregulatory Cytokines

HIV-1 Tat Protein Induces Production of Proinflammatory Cytokines by Human Dendritic Cells and Monocytes/Macrophages through Engagement of TLR4-MD2-CD14 Complex and Activation of NF-κB Pathway

HIV Infection «HIV Tat Protein, a Key Factor in Pathogenesis and Immune System Dysregulation: Implication of IL-10»

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