Cooperative induction of CXCL10 involves NADPH oxidase: Implications for HIV dementia

Rachel Williams, Honghong Yao, Fuwang Peng, Yanjing Yang, Crystal Bethel-Brown, Shilpa J Buch

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

With the increasing prevalence of HIV-associated neurocognititve disorders (HAND), understanding the mechanisms by which HIV-1 induces neuro-inflammation and subsequent neuronal damage is important. The hallmark features of HIV-encephalitis, the pathological correlate of HIV-associated Dementia (HAD), are gliosis, oxidative stress, chemokine dysregulation, and neuronal damage/death. Since neurons are not infected by HIV-1, the current thinking is that these cells are damaged indirectly by pro-inflammatory chemokines released by activated glial cells. CXCL10 is a neurotoxic chemokine that is upregulated in astroglia activated by HIV-1 Tat, IFN-γ, and TNF-α. In this study we have demonstrated that HIV-1 Tat increases CXCL10 expression in IFN-γ and TNF-α stimulated human astrocytes via NADPH oxidase. We have shown that the treatment of astrocytes with a mixture of Tat and cytokines leads to a respiratory burst that is abrogated by apocynin, an NADPH oxidase inhibitor. Pretreatment of Tat, IFN-γ, and TNF-α stimulated astrocytes with apocynin also resulted in concomitant inhibition of CXCL10 expression. Additionally, apocynin was also able to reduce Tat and cytokine-mediated activation of the corresponding signaling molecules Erk1/2, Jnk, and Akt with a decrease in activation and nuclear translocation of NF-κB, important regulators of CXCL10 induction. Understanding the mechanisms involved in reducing both oxidative stress and the release of pro-inflammatory agents could lead to the development of therapeutics aimed at decreasing neuro-inflammation in patients suffering from HAD.

Original languageEnglish (US)
Pages (from-to)611-621
Number of pages11
JournalGlia
Volume58
Issue number5
DOIs
StatePublished - Apr 1 2010

Fingerprint

AIDS Dementia Complex
NADPH Oxidase
Astrocytes
HIV-1
Chemokines
Oxidative Stress
HIV
Cytokines
Inflammation
Gliosis
Respiratory Burst
Encephalitis
Neuroglia
Neurons
Therapeutics
acetovanillone

Keywords

  • Astrocytes
  • CXCL10
  • HIV-associated dementia
  • NADPH oxidase

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Cooperative induction of CXCL10 involves NADPH oxidase : Implications for HIV dementia. / Williams, Rachel; Yao, Honghong; Peng, Fuwang; Yang, Yanjing; Bethel-Brown, Crystal; Buch, Shilpa J.

In: Glia, Vol. 58, No. 5, 01.04.2010, p. 611-621.

Research output: Contribution to journalArticle

Williams, R, Yao, H, Peng, F, Yang, Y, Bethel-Brown, C & Buch, SJ 2010, 'Cooperative induction of CXCL10 involves NADPH oxidase: Implications for HIV dementia', Glia, vol. 58, no. 5, pp. 611-621. https://doi.org/10.1002/glia.20949
Williams, Rachel ; Yao, Honghong ; Peng, Fuwang ; Yang, Yanjing ; Bethel-Brown, Crystal ; Buch, Shilpa J. / Cooperative induction of CXCL10 involves NADPH oxidase : Implications for HIV dementia. In: Glia. 2010 ; Vol. 58, No. 5. pp. 611-621.
@article{93a1606da01444ed8ca9a9a17b5765a3,
title = "Cooperative induction of CXCL10 involves NADPH oxidase: Implications for HIV dementia",
abstract = "With the increasing prevalence of HIV-associated neurocognititve disorders (HAND), understanding the mechanisms by which HIV-1 induces neuro-inflammation and subsequent neuronal damage is important. The hallmark features of HIV-encephalitis, the pathological correlate of HIV-associated Dementia (HAD), are gliosis, oxidative stress, chemokine dysregulation, and neuronal damage/death. Since neurons are not infected by HIV-1, the current thinking is that these cells are damaged indirectly by pro-inflammatory chemokines released by activated glial cells. CXCL10 is a neurotoxic chemokine that is upregulated in astroglia activated by HIV-1 Tat, IFN-γ, and TNF-α. In this study we have demonstrated that HIV-1 Tat increases CXCL10 expression in IFN-γ and TNF-α stimulated human astrocytes via NADPH oxidase. We have shown that the treatment of astrocytes with a mixture of Tat and cytokines leads to a respiratory burst that is abrogated by apocynin, an NADPH oxidase inhibitor. Pretreatment of Tat, IFN-γ, and TNF-α stimulated astrocytes with apocynin also resulted in concomitant inhibition of CXCL10 expression. Additionally, apocynin was also able to reduce Tat and cytokine-mediated activation of the corresponding signaling molecules Erk1/2, Jnk, and Akt with a decrease in activation and nuclear translocation of NF-κB, important regulators of CXCL10 induction. Understanding the mechanisms involved in reducing both oxidative stress and the release of pro-inflammatory agents could lead to the development of therapeutics aimed at decreasing neuro-inflammation in patients suffering from HAD.",
keywords = "Astrocytes, CXCL10, HIV-associated dementia, NADPH oxidase",
author = "Rachel Williams and Honghong Yao and Fuwang Peng and Yanjing Yang and Crystal Bethel-Brown and Buch, {Shilpa J}",
year = "2010",
month = "4",
day = "1",
doi = "10.1002/glia.20949",
language = "English (US)",
volume = "58",
pages = "611--621",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Cooperative induction of CXCL10 involves NADPH oxidase

T2 - Implications for HIV dementia

AU - Williams, Rachel

AU - Yao, Honghong

AU - Peng, Fuwang

AU - Yang, Yanjing

AU - Bethel-Brown, Crystal

AU - Buch, Shilpa J

PY - 2010/4/1

Y1 - 2010/4/1

N2 - With the increasing prevalence of HIV-associated neurocognititve disorders (HAND), understanding the mechanisms by which HIV-1 induces neuro-inflammation and subsequent neuronal damage is important. The hallmark features of HIV-encephalitis, the pathological correlate of HIV-associated Dementia (HAD), are gliosis, oxidative stress, chemokine dysregulation, and neuronal damage/death. Since neurons are not infected by HIV-1, the current thinking is that these cells are damaged indirectly by pro-inflammatory chemokines released by activated glial cells. CXCL10 is a neurotoxic chemokine that is upregulated in astroglia activated by HIV-1 Tat, IFN-γ, and TNF-α. In this study we have demonstrated that HIV-1 Tat increases CXCL10 expression in IFN-γ and TNF-α stimulated human astrocytes via NADPH oxidase. We have shown that the treatment of astrocytes with a mixture of Tat and cytokines leads to a respiratory burst that is abrogated by apocynin, an NADPH oxidase inhibitor. Pretreatment of Tat, IFN-γ, and TNF-α stimulated astrocytes with apocynin also resulted in concomitant inhibition of CXCL10 expression. Additionally, apocynin was also able to reduce Tat and cytokine-mediated activation of the corresponding signaling molecules Erk1/2, Jnk, and Akt with a decrease in activation and nuclear translocation of NF-κB, important regulators of CXCL10 induction. Understanding the mechanisms involved in reducing both oxidative stress and the release of pro-inflammatory agents could lead to the development of therapeutics aimed at decreasing neuro-inflammation in patients suffering from HAD.

AB - With the increasing prevalence of HIV-associated neurocognititve disorders (HAND), understanding the mechanisms by which HIV-1 induces neuro-inflammation and subsequent neuronal damage is important. The hallmark features of HIV-encephalitis, the pathological correlate of HIV-associated Dementia (HAD), are gliosis, oxidative stress, chemokine dysregulation, and neuronal damage/death. Since neurons are not infected by HIV-1, the current thinking is that these cells are damaged indirectly by pro-inflammatory chemokines released by activated glial cells. CXCL10 is a neurotoxic chemokine that is upregulated in astroglia activated by HIV-1 Tat, IFN-γ, and TNF-α. In this study we have demonstrated that HIV-1 Tat increases CXCL10 expression in IFN-γ and TNF-α stimulated human astrocytes via NADPH oxidase. We have shown that the treatment of astrocytes with a mixture of Tat and cytokines leads to a respiratory burst that is abrogated by apocynin, an NADPH oxidase inhibitor. Pretreatment of Tat, IFN-γ, and TNF-α stimulated astrocytes with apocynin also resulted in concomitant inhibition of CXCL10 expression. Additionally, apocynin was also able to reduce Tat and cytokine-mediated activation of the corresponding signaling molecules Erk1/2, Jnk, and Akt with a decrease in activation and nuclear translocation of NF-κB, important regulators of CXCL10 induction. Understanding the mechanisms involved in reducing both oxidative stress and the release of pro-inflammatory agents could lead to the development of therapeutics aimed at decreasing neuro-inflammation in patients suffering from HAD.

KW - Astrocytes

KW - CXCL10

KW - HIV-associated dementia

KW - NADPH oxidase

UR - http://www.scopus.com/inward/record.url?scp=77749339868&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77749339868&partnerID=8YFLogxK

U2 - 10.1002/glia.20949

DO - 10.1002/glia.20949

M3 - Article

C2 - 19941336

AN - SCOPUS:77749339868

VL - 58

SP - 611

EP - 621

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 5

ER -