Regulation of TNFα and TGFβ-1 gene transcription by HIV-1 Tat in CNS cells

Sawaya, Bassel E.; Thatikunta, Prakash; Denisova, L. Ya.; Brady, John; Khalili, Kamel; Amini, Shohreh

doi:10.1016/s0165-5728(98)00044-7

Cited by 61 publications

(40 citation statements)

References 64 publications

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“…Early studies indicated that in cells derived from CNS, Tat has the ability to stimulate the HIV-1 LTR in the absence of TAR [24,25]. TAR-independent activity of Tat may be the result of cytokine activation, as in earlier studies, TNF-␣ mRNA has been shown to be increased by Tat [20,21]. It is of note that TNF-␣ activates transcription of the HIV-1 LTR via activation of cytoplasmic nuclear factor-B (NF-B) [26].…”

Section: Role Of Tat and Cytokine Dysregulation By Hiv In Cnsmentioning

confidence: 98%

Molecular pathway involved in HIV-1-induced CNS pathology: role of viral regulatory protein, Tat

Rappaport

Joseph

Croul

et al. 1999

Journal of Leukocyte Biology

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161

125

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Section: Role Of Tat and Cytokine Dysregulation By Hiv In Cnsmentioning

confidence: 98%

Molecular pathway involved in HIV-1-induced CNS pathology: role of viral regulatory protein, Tat

Rappaport

Joseph

Croul

et al. 1999

Journal of Leukocyte Biology

Self Cite

161

125

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“…HIV tat protein has been linked to high TGF-b secretion in infected cells Zauli et al 1992;Lotz et al 1994;Sawaya et al 1998;Reinhold et al 1999). The association of viral gp160 with CD4 on monocytes can also induce TGF-b production (Hu et al 1996).…”

Section: Viralmentioning

confidence: 99%

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Sanjabi

2017

Cold Spring Harb Perspect Biol

451

306

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Transforming growth factor b (TGF-b) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-b alters immunity under various conditions. Under steady-state conditions, TGF-b regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-b inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral ( p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges. Similarly, TGF-b controls the proliferation, survival, activation, and differentiation of B cells, as well as the development and functions of innate cells, including natural killer (NK) cells, macrophages, dendritic cells, and granulocytes. Collectively, TGF-b plays a pivotal role in maintaining peripheral tolerance against self-and innocuous antigens, such as food, commensal bacteria, and fetal alloantigens, and in controlling immune responses to pathogens.

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“…In keeping with this, Tat exerts transcriptional control over numerous cellular genes in a variety of cell types (1,3), and it increases TNF-␣ expression in neuronal cells at the transcriptional level (3); this in turn leads to an increase in platelet-activating factor (PAF) production by mononuclear phagocytes (4). Furthermore, Tat has been shown to have a number of direct effects on neurons, including excessive depolarization and calcium influx (5) as well as apoptosis (5,6).…”

Section: T Ransactivator Of Transcription Protein (Tat)mentioning

confidence: 99%

HIV-1 Transactivator of Transcription Protein Induces Mitochondrial Hyperpolarization and Synaptic Stress Leading to Apoptosis

Perry

Norman

Litzburg³

et al. 2005

The Journal of Immunology

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Despite the efficacy of highly active antiretroviral therapy in reducing viral burden, neurologic disease associated with HIV-1 infection of the CNS has not decreased in prevalence. HIV-1 does not induce disease by direct infection of neurons, although extensive data suggest that intra-CNS viral burden correlates with both the severity of virally induced neurologic disease, and with the generation of neurotoxic metabolites. Many of these molecules are capable of inducing neuronal apoptosis in vitro, but neuronal apoptosis in vivo does not correlate with CNS dysfunction, thus prompting us to investigate cellular and synaptic events occurring before cell death that may contribute to HIV-1-associated neurologic disease. We now report that the HIV-1 regulatory protein transactivator of transcription protein (Tat) increased oxidative stress, ATP levels, and mitochondrial membrane potential in primary rodent cortical neurons. Additionally, a proinflammatory cellular metabolite up-regulated by Tat, platelet-activating factor, also induced oxidative stress and mitochondrial hyperpolarization in neurons, suggesting that this type of metabolic dysfunction may occur on a chronic basis during HIV-1 infection of the CNS. Tat-induced mitochondrial hyperpolarization could be blocked with a low dose of the protonophore FCCP, or the mitochondrial KATP channel antagonist, tolbutamide. Importantly, blocking the mitochondrial hyperpolarization attenuated Tat-induced neuronal apoptosis, suggesting that increased mitochondrial membrane potential may be a causal event in precipitating neuronal apoptosis in cell culture. Finally, Tat and platelet-activating factor also increased neuronal vesicular release, which may be related to increased mitochondrial bioenergetics and serve as a biomarker for early damage to neurons.

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Regulation of TNFα and TGFβ-1 gene transcription by HIV-1 Tat in CNS cells

Cited by 61 publications

References 64 publications

Molecular pathway involved in HIV-1-induced CNS pathology: role of viral regulatory protein, Tat

Molecular pathway involved in HIV-1-induced CNS pathology: role of viral regulatory protein, Tat

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

HIV-1 Transactivator of Transcription Protein Induces Mitochondrial Hyperpolarization and Synaptic Stress Leading to Apoptosis

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