The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-α

Yeung, Michael C.; Pulliam, Lynn; Lau, Alan F.

doi:10.1097/00002030-199502000-00004

Cited by 82 publications

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“…Although the mechanisms underlying HIV-induced cell death in the nervous system are not fully understood, results presented herein suggest that underlying neurotoxic pathways are highly complex and likely to differ for each viral protein. HIV-1 viral products can be released by infected microglia and astroglia (Ensoli et al, 1990;Munis et al, 1992;Robert-Guroff et al, 1990;Chang et al, 1997;Shutt and Soil, 1999;Jones et al, 1998;Jones et al, 2000), and can also induce the production and release of proinflammatory cytokines and cellular toxins in neural cells (Yeung et al, 1995;Adamson et al, 1996;Bagetta et al, 1996a;Kaul and Lipton, 1999;Nath et al, 1999). Numerous lines of evidence suggest that extracellular proinflammatory cytokines and cellular toxins can induce neuronal apoptosis (Gabuzda et al, 1986;Gendelman et al, 1994;Shi et al, 1998;New et al, 1998;Bagetta et al, 1999;Holden et al, 1999;Zheng et al, 1999;Park et al, 2001;Takahashi et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…HIV-1 is neurotoxic by inducing inflammation and through the direct release of toxic viral proteins such as Nef, Vpr, gp120 and Tat (Haughey et al, 2001;Brenneman et al, 1988;Dreyer et al, 1990;Adamson et al, 1996;New et al, 1997;Kruman et al, 1998;Yeung et al, 1998;Huang and Bond, 2000;Trillo-Pazos et al, 2000;Nath, 2002). The neurotoxicity of gp120 has been demonstrated both in primary human neuronal cultures (Lannuzel et al, 1997;Yeung et al, 1995) and in transgenic mice (Toggas et al, 1994). Gp120 is thought to be intrinsically neurotoxic through an apoptotic mechanism (Barillari et al, 1993;Albini et al, 1996a,b;Bagetta et al, 1996b;Hesselgesser et al, 1998;Marzo et al, 1998;Meucci et al, 1998;Zheng et al, 1999) and may also act via inflammatory cytokines (Bagetta et al, 1996a(Bagetta et al, , 1999Lipton, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Apoptotic death of striatal neurons induced by human immunodeficiency virus-1 Tat and gp120: Differential involvement of caspase-3 and endonuclease G

et al. 2004

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apoptotic death of striatal neurons induced by human immunodeficiency virus-1 Tat and gp120: Differential involvement of caspase-3 and endonuclease G

et al. 2004

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“…The cytokines promote dysmyelination and inflammation, and neurological symptoms result. It seems that the HIV envelope protein gp120 is toxic to human brain cell cultures through induction of TNF-␣ and interleukin 6 (Yeung et al, 1995). It has been known for some time that portions of the HIV envelope protein induce TNF-␣ in primary brain culture (Merrill et al, 1992).…”

Section: Abstract: ␣-Msh; Tnf-␣ ; Modulation Of Cns Inflammation; Nementioning

confidence: 99%

α-MSH Modulates Local and Circulating Tumor Necrosis Factor-α in Experimental Brain Inflammation

et al. 1997

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Tumor necrosis factor (TNF-α) underlies pathological processes and functional disturbances in acute and chronic neurological disease and injury. The neuroimmunomodulatory peptide α-MSH modulates actions and production of proinflammatory cytokines including TNF-α, but there is no prior evidence that it alters TNF-α induced within the brain. To test for this potential influence of the peptide, TNF-α was induced centrally by local injection of bacterial lipopolysaccharide (LPS). α-MSH given once i.c.v. with LPS challenge, twice daily intraperitoneally (i.p.) for 5 d between central LPS injections, or both i.p. and centrally, inhibited production of TNF-α within brain tissue. Inhibition of TNF-α protein formation by α-MSH was confirmed by inhibition of TNF-α mRNA. Plasma TNF-α concentration was elevated markedly after central LPS, indicative of an augmented peripheral host response induced by the CNS signal. The increase was inhibited by α-MSH treatments, in relation to inhibition of central TNF-α. Presence within normal mouse brain of mRNA for the α-MSH receptor MC-1 suggests that the inhibitory effects of α-MSH on brain and plasma TNF-α might be mediated by this receptor subtype. The inhibitory effect of α-MSH on brain TNF-α did not depend on circulating factors because the effect also occurred in brain tissuein vitro. This indicates that α-MSH can act directly on brain cells to inhibit their production of TNF-α. If central TNF-α contributes to pathology in CNS disease and injury, and promotes inflammation in the periphery, agents that act on brain α-MSH receptors should decrease the pathological TNF-α reaction and promote tissue survival.

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“…Whereas TNF-␣ has been suggested to be toxic to neurons (11)(12)(13) and glia (14), it has also been reported to prevent cell death in vitro after exposure of neurons to ␤-amyloid peptide (15) and in vivo after administration of excitotoxins (16), peripheral nerve injury (17), and cerebral ischemia (18). TNF-␣ has also been associated with the regulation of tissue remodeling, gliosis, and scar formation (19)(20)(21).…”

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confidence: 99%

Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury

Scherbel

Raghupathi

Nakamura

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

375

231

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The present study evaluated behavioral and histopathological outcome after controlled cortical impact (CCI) brain injury in mice deficient in tumor necrosis factor [TNF(؊/؊)] and their wild-type (wt) littermates. Mice were subjected to CCI brain injury [TNF(؊/؊), n ‫؍‬ 10; wt, n ‫؍‬ 10] or served as uninjured controls [TNF(؊/؊), n ‫؍‬ 10; wt, n ‫؍‬ 10] and were evaluated for deficits in memory retention at 7 days postinjury. Although both brain-injured wt and TNF(؊/؊) mice exhibited significant memory dysfunction compared to uninjured controls (P < 0.02), the deficits in memory retention in injured TNF(؊/؊) mice were significantly less severe than in injured wt mice (P < 0.02). A second group of mice was subjected to CCI brain injury [TNF(؊/؊), n ‫؍‬ 20; wt, n ‫؍‬ 20] or served as uninjured controls [TNF(؊/؊), n ‫؍‬ 15; wt, n ‫؍‬ 15] and were evaluated over a 4-week period for neurological motor function. In the acute posttraumatic period (48 h postinjury), braininjured TNF(؊/؊) mice were significantly less impaired than injured wt mice on composite neuroscore (P < 0.001), rotarod (P < 0.05), and beam balance (P < 0.02) tests. However, wt mice recovered from brain injury by 2-3 weeks postinjury, whereas TNF(؊/؊) mice continued to demonstrate persistent motor deficits up to 4 weeks postinjury. Histopathological analysis at 2 and 4 weeks postinjury revealed that brain-injured TNF(؊/؊) mice had significantly more cortical tissue loss than wt mice (P < 0.02). Our results suggest that although the presence of TNF in the acute posttraumatic period may be deleterious, this cytokine may play a role in facilitating long-term behavioral recovery and histological repair after brain injury.

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The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-α

Cited by 82 publications

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Apoptotic death of striatal neurons induced by human immunodeficiency virus-1 Tat and gp120: Differential involvement of caspase-3 and endonuclease G

Apoptotic death of striatal neurons induced by human immunodeficiency virus-1 Tat and gp120: Differential involvement of caspase-3 and endonuclease G

α-MSH Modulates Local and Circulating Tumor Necrosis Factor-α in Experimental Brain Inflammation

Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury

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