Effect of azidothymidine (AZT) on P24 antigen levels in patients with AIDS‐related complex and AIDS

Reddy, Mohan M.; McKinley, George; Englard, Arthur; Grieco, Michael H.

doi:10.1002/jcla.1860030402

Cited by 8 publications

(6 citation statements)

References 14 publications

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“…At the time U937 cells were added to the Transwell systems, cell culture media from infected cultures were collected, and p24 levels were determined by ELISA. p24 levels were at the level of 75 pg/ml, which corresponds to that present in serum of patients with AIDS (28, 29).…”

Section: Methodsmentioning

confidence: 84%

PPARα and PPARγ protect against HIV‐1‐induced MMP‐9 overexpression via caveolae‐associated ERK and Akt signaling

et al. 2011

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Activation of matrix metalloproteinase-9 (MMP-9) is involved in HIV-1-induced disruption of the blood-brain barrier (BBB). In the present study, we hypothesize that peroxisome proliferator-activated receptor (PPAR)-α or PPARγ can protect against HIV-1-induced MMP-9 overexpression in brain endothelial cells (hCMEC cell line) by attenuating cellular oxidative stress and down-regulation of caveolae-associated redox signaling. Exposure to HIV-1-infected monocytes induced phosphorylation of ERK1/2 and Akt in hCMEC by 2.5- and 3.6-fold, respectively; however, these effects were attenuated by overexpression of PPARα or PPARγ and by silencing of caveolin-1 (cav-1). Coculture of hCMEC with HIV-1-infected monocytes significantly induced MMP-9 promoter and enzyme activity by 3- to 3.5-fold. Promoter mutation studies indicated that SP-1 (g1940t_g1941t) is an essential transcription factor involved in induction of MMP-9 promoter by HIV-1. In addition, HIV-1-stimulated activity of MMP-9 promoter was inhibited by mutation of AP-1 site 2 (c1918t_a1919g) and both (but not individual) NF-κB binding sites (g1389c and g1664c). PPAR overexpression, ERK1/2 or Akt inhibition, and silencing of cav-1 all effectively protected against HIV-1-induced MMP-9 promoter activity, indicating a close relationship among HIV-1-induced cerebrovascular toxicity, redox-regulated mechanisms, and functional caveolae. Such a link was further confirmed in MMP-9-deficient mice exposed to PPARα or PPARγ agonist and injected with the HIV-1-specific protein Tat into cerebral vasculature. Overall, our results indicate that ERK1/2, Akt, and cav-1 are involved in the regulatory mechanisms of PPAR-mediated protection against HIV-1-induced MMP-9 expression in brain endothelial cells.

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Section: Methodsmentioning

confidence: 84%

PPARα and PPARγ protect against HIV‐1‐induced MMP‐9 overexpression via caveolae‐associated ERK and Akt signaling

et al. 2011

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“…Cells were then washed, resuspended in fresh medium, and maintained for an additional 3-5 days to facilitate viral replication. The levels of HIV p24 used in all experiments in the present study were between 140 -180 g/l, which correspond to those present in serum of AIDS patients (34,35). Uninfected U937 cells served as controls.…”

Section: Hiv-1 Stock Generation and Monocyte Infectionmentioning

confidence: 98%

PPARα and PPARγ attenuate HIV‐induced dysrégulation of tight junction proteins by modulations of matrix metalloproteinase and proteasome activities

et al. 2009

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The blood-brain barrier (BBB) plays an important role in HIV trafficking into the brain and the development of the central nervous system complications in HIV infection. Tight junctions are the main structural and functional elements that regulate the BBB integrity. Exposure of human brain microvascular endothelial cells (hCMEC/D3 cell line) to HIV-infected monocytes resulted in decreased expression of tight junction proteins, such as junctional adhesion molecule-A (JAM)-A, occludin, and zonula occludens (ZO)-1. Control experiments involved exposure to uninfected monocytes. Alterations of tight junction protein expression were associated with increased endothelial permeability and elevated transendothelial migration of HIV-infected monocytes across an in vitro model of the BBB. Notably, overexpression of the peroxisome proliferator-activated receptor (PPAR)alpha or PPARgamma attenuated HIV-mediated dysregulation of tight junction proteins. With the use of exogenous PPARgamma agonists and silencing of PPARalpha or PPARgamma, these protective effects were connected to down-regulation of matrix metalloproteinase (MMP) and proteasome activities. Indeed, the HIV-induced decrease in the expression of JAM-A and occludin was restored by inhibition of MMP activity. Moreover, both MMP and proteasome inhibitors attenuated HIV-mediated altered expression of ZO-1. The present data indicate that down-regulation of MMP and proteasome activities constitutes a novel mechanism of PPAR-induced protections against HIV-induced disruption of brain endothelial cells.

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“…In our study of ZDV, we previously have reported that we could not detect HIV p24 antigen utilizing HIV p24 antigen assay obtained from Abbott Laboratories in 8 patients (4 ARC and 4 AIDS) out of 20 (8). By utilizing a highly sensitive HIV p24 antigen assay developed at Immunodiagnostic Laboratories preceded by treatment with HCl to denature antibody and probably freeing antigen sequestered in immune complexes, we were able to detect HIV p24 antigen in all Figure 2.…”

Section: Resultsmentioning

confidence: 73%

“…All the serum samples from each patient were tested simultaneously in two assays. The standard assay for HIV p24 antigen levels was a sandwich solid phase enzyme immunoassay method (Abbott Laboratories) with results expressed as pg/ml (8). This assay is sensitive to antigen concentrations of SO -t 20 pg/ml.…”

Section: Methodsmentioning

confidence: 99%

An improved method for monitoring efficacy of anti‐retroviral therapy in HIV‐infected individuals: A highly sensitive HIV p24 antigen assay

Reddy¹,

Winger²,

Hargrove³

et al. 1992

Clinical Laboratory Analysis

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Circulating human immunodeficiency virus (HIV) p24 antigen levels were measured by a highly sensitive HIV p24 antigen-capture enzyme-linked immunosorbent assay (ELISA) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) otherwise negative for HIV p24 antigen measured by a commercial antigen-capture ELISA. The assays were performed at baseline and at several intervals during treatment with either zidovudine (ZDV) or dideoxyinosine (ddl). To further enhance the rate of antigen detection, serum was pretreated with hydrochloric acid to denature antibody in immune complexes. Utilizing this assay system, we monitored these patients for drug efficacy. HIV p24 antigen levels obtained by using this sensitive assay decreased in 3 of 8 patients receiving ZDV during 8 weeks of ZDV treatment. Similarly, ddl administration was associated with a decrease of HIV p24 antigen levels in 3 of 5 patients. Thus, the use of the highly sensitive HIV p24 antigen assay permitted the monitoring of surrogate HIV p24 antigen as a measure of efficacy of anti-retroviral therapy in all of these patients who were otherwise HIV p24 antigen-negative at the onset of anti-retroviral therapy.

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Effect of azidothymidine (AZT) on P24 antigen levels in patients with AIDS‐related complex and AIDS

Cited by 8 publications

References 14 publications

PPARα and PPARγ protect against HIV‐1‐induced MMP‐9 overexpression via caveolae‐associated ERK and Akt signaling

PPARα and PPARγ protect against HIV‐1‐induced MMP‐9 overexpression via caveolae‐associated ERK and Akt signaling

PPARα and PPARγ attenuate HIV‐induced dysrégulation of tight junction proteins by modulations of matrix metalloproteinase and proteasome activities

An improved method for monitoring efficacy of anti‐retroviral therapy in HIV‐infected individuals: A highly sensitive HIV p24 antigen assay

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