Alteration of blood brain barrier permeability by T-2 toxin: Role of MMP-9 and inflammatory cytokines

Ravindran, Jayaraj; Agrawal, Mona; Gupta, Nimesh; Rao, P. Venkata

doi:10.1016/j.tox.2010.11.006

Cited by 69 publications

(43 citation statements)

References 43 publications

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“…When combining the observations that PAR inhibits IjB-a degradation and NFjB transcriptional activity as result of IL-1a and TNF-a induction together, there is a high probability that the classical pathway of NF-jB activation is what drives MMP-9 synthesis upregulation. These results correlate with findings of other studies which show that MMP-9 is induced by inflammatory mediators [39]. MMP-2 levels remained unchanged during all the experiments, both in gel zymography and in the immunocytochemistry.…”

Section: Discussionsupporting

confidence: 91%

The involvement of oxidants and NF-κB in cytokine-induced MMP-9 synthesis by bone marrow-derived osteoprogenitor cells

2012

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Section: Discussionsupporting

confidence: 91%

The involvement of oxidants and NF-κB in cytokine-induced MMP-9 synthesis by bone marrow-derived osteoprogenitor cells

2012

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“…TNF-a and IL-1b have been shown to be major inducers of brain endothelium activation and responsible for the increase in endothelial permeability of the BBB (29)(30)(31). Because both cytokines are produced upon infection of astrocytes and microglia with B. abortus (10), we decided to investigate their role in the activation of HBMEC by Brucella-infected glial cells by first focusing on IL1-b.…”

Section: Activation Of Hbmec By Glial Cells Is Mediated By Brucella-imentioning

confidence: 99%

Glial Cell–Elicited Activation of Brain Microvasculature in Response to Brucella abortus Infection Requires ASC Inflammasome–Dependent IL-1β Production

Miraglia

Franco

Rodrı́guez

et al. 2016

The Journal of Immunology

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Blood–brain barrier activation and/or dysfunction are a common feature of human neurobrucellosis, but the underlying pathogenic mechanisms are largely unknown. In this article, we describe an immune mechanism for inflammatory activation of human brain microvascular endothelial cells (HBMEC) in response to infection with Brucella abortus. Infection of HBMEC with B. abortus induced the secretion of IL-6, IL-8, and MCP-1, and the upregulation of CD54 (ICAM-1), consistent with a state of activation. Culture supernatants (CS) from glial cells (astrocytes and microglia) infected with B. abortus also induced activation of HBMEC, but to a greater extent. Although B. abortus–infected glial cells secreted IL-1β and TNF-α, activation of HBMEC was dependent on IL-1β because CS from B. abortus–infected astrocytes and microglia deficient in caspase-1 and apoptosis-associated speck-like protein containing a CARD failed to induce HBMEC activation. Consistently, treatment of CS with neutralizing anti–IL-1β inhibited HBMEC activation. Both absent in melanoma 2 and Nod-like receptor containing a pyrin domain 3 are partially required for caspase-1 activation and IL-1β secretion, suggesting that multiple apoptosis-associated speck-like protein containing CARD–dependent inflammasomes contribute to IL-1β–induced activation of the brain microvasculature. Inflammasome-mediated IL-1β secretion in glial cells depends on TLR2 and MyD88 adapter-like/TIRAP. Finally, neutrophil and monocyte migration across HBMEC monolayers was increased by CS from Brucella-infected glial cells in an IL-1β–dependent fashion, and the infiltration of neutrophils into the brain parenchyma upon intracranial injection of B. abortus was diminished in the absence of Nod-like receptor containing a pyrin domain 3 and absent in melanoma 2. Our results indicate that innate immunity of the CNS set in motion by B. abortus contributes to the activation of the blood–brain barrier in neurobrucellosis and IL-1β mediates this phenomenon.

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“…Previous studies have demonstrated that satratoxins possess direct neurotoxic effects, resulting in neuronal cell death and neuroinflammation (Corps et al, 2010;Pestka et al, 2008a). Although studies have demonstrated that trichothecenes, including DON, could cross the blood-brain barrier, accumulate in the brain and cause neurologic disorders (Pestka et al, 2008b;Ravindran et al, 2011), no evaluations of their effect on astrocytes or microglia have been conducted. In the present study, we investigated the effect of the ribotoxin DON on the viability and functions of astrocytic and microglial cells of animal and human origin.…”

Section: Introductionmentioning

confidence: 99%

The ribotoxin deoxynivalenol affects the viability and functions of glial cells

Razafimanjato

Benzaria

Taïeb

et al. 2011

Glia

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Glial cells are responsible for maintaining brain homeostasis. Modification of the viability and functions of glial cells, including astrocytes and microglia, are associated with neuronal death and neurological diseases. Many toxins (heavy metals, pesticides, bacterial or viral toxins) are known to impact on brain cell viability and functions. Although recent publications suggest a potential link between environmental exposure of humans to mycotoxins and neurological diseases, data regarding the effects of fungal toxins on brain cells are scarce. In the present study, we looked at the impact of deoxynivalenol (DON), a fungal ribotoxin, on glial cells from animal and human origin. We found that DON decreased the viability of glial cells with a higher toxicity against microglial cells compared with astrocytes. In addition to cellular toxicity, DON affected key functions of glial cells. Thus, DON caused a biphasic effect on the neuroinflammatory response of microglia to lipopolysaccharide (LPS), while sublethal doses of DON increased the LPS-induced secretion of TNF-α and nitric oxide, toxic doses inhibited it. In addition to affecting microglial functions, sublethal doses of DON also suppressed the uptake of L-glutamate by astrocytes. This inhibition was associated with a modification of the expression of the glutamate transporters at the plasma membrane. Our results suggest that environmental ribotoxins such as DON could, at low doses, cause modifications of brain homeostasis and possibly participate in the etiology of neurological diseases in which alterations of the glia are involved.

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Alteration of blood brain barrier permeability by T-2 toxin: Role of MMP-9 and inflammatory cytokines

Cited by 69 publications

References 43 publications

The involvement of oxidants and NF-κB in cytokine-induced MMP-9 synthesis by bone marrow-derived osteoprogenitor cells

The involvement of oxidants and NF-κB in cytokine-induced MMP-9 synthesis by bone marrow-derived osteoprogenitor cells

Glial Cell–Elicited Activation of Brain Microvasculature in Response to Brucella abortus Infection Requires ASC Inflammasome–Dependent IL-1β Production

The ribotoxin deoxynivalenol affects the viability and functions of glial cells

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