Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with β-amyloid[25–35]

Meda, Lucia; Baron, Pierluigi; Prat, Elisabetta; Scarpini, Elio; Scarlato, G.; Cassatella, Marco A.; Rossi, Filippo

doi:10.1016/s0165-5728(98)00188-x

Cited by 141 publications

(123 citation statements)

References 39 publications

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“…8A-C) then leads to the release of TNF-␣ and IL-1␤ (interleukin-1␤), which are known to activate astroglial Cx43 hemichannels (Retamal et al, 2007). In addition, these cytokines are produced by A␤-treated microglia (Meda et al, 1999) and their mRNA expression is increased in these cells at amyloid plaques (Hickman et al, 2008). Accordingly, astroglial hemichannel activity could be triggered directly by action of A␤ [25][26][27][28][29][30][31][32][33][34][35] and by the release of proinflammatory cytokines from microglia (Fig.…”

Section: A␤-induced Neuronal Death Occurs Through a Sequence Of Hemicmentioning

confidence: 99%

Amyloid β-Induced Death in Neurons Involves Glial and Neuronal Hemichannels

et al. 2011

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The mechanisms involved in Alzheimer's disease are not completely understood and how glial cells contribute to this neurodegenerative disease remains to be elucidated. Because inflammatory treatments and products released from activated microglia increase glial hemichannel activity, we investigated whether amyloid-␤ peptide (A␤) could regulate these channels in glial cells and affect neuronal viability. Microglia, astrocytes, or neuronal cultures as well as acute hippocampal slices made from GFAP-eGFP transgenic mice were treated with the active fragment of A␤. Hemichannel activity was monitored by single-channel recordings and by time-lapse ethidium uptake, whereas neuronal death was assessed by Fluoro-Jade C staining. We report that low concentrations of A␤ 25-35 increased hemichannel activity in all three cell types and microglia initiate these effects triggered by A␤. Finally, neuronal damage occurs by activation of neuronal hemichannels induced by ATP and glutamate released from A␤ 25-35 -activated glia. These responses were observed in the presence of external calcium and were differently inhibited by hemichannel blockers, whereas the A␤ 25-35 -induced neuronal damage was importantly reduced in acute slices made from Cx43 knock-out mice. Thus, A␤ leads to a cascade of hemichannel activation in which microglia promote the release of glutamate and ATP through glial (microglia and astrocytes) hemichannels that induces neuronal death by triggering hemichannels in neurons. Consequently, this work opens novel avenues for alternative treatments that target glial cells and neurons to maintain neuronal survival in the presence of A␤.

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Section: A␤-induced Neuronal Death Occurs Through a Sequence Of Hemicmentioning

confidence: 99%

Amyloid β-Induced Death in Neurons Involves Glial and Neuronal Hemichannels

et al. 2011

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“…23,24) Various protein kinases affect each other, that is, "cross talk" of intracellular signaling occurs. 25) reported that the fragment Ab [25][26][27][28][29][30][31][32][33][34][35] triggers the release of NO and TNFa from cultured microglia. Ab-stimulated microglia also release IL-1b.…”

Section: Microglial Activation In Various Neuro-logical Diseasesmentioning

confidence: 99%

“…Ab-stimulated microglia also release IL-1b. 26,27) Ab peptides stimulate the production of O 2 Ϫ and the production is inhibited by inhibitors of tyrosine kinases or phosphatidylinositol 3-kinase and by dibutyryl cAMP (dbcAMP), and is potentiated by IFNg or TNFa. 28) Ab peptides have other activity in addition to microglial activation, such as inducing the outward rectifying K channel 29) and elevating intracellular Ca 2ϩ level.…”

Section: Microglial Activation In Various Neuro-logical Diseasesmentioning

confidence: 99%

Regulating Factors for Microglial Activation.

Nakamura

2002

Biological & Pharmaceutical Bulletin

219

114

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“…In response to A␤, microglia secrete a range of proinflammatory molecules including cytokines (Meda et al, 1999) and reactive oxygen species (ROS) (Bianca et al, 1999). Oxidative damage is a feature of the AD brain (Lyras et al, 1997), and considerable evidence suggests oxidative stress induced by microglial-derived ROS is a major contributor to neurodegeneration (Wilkinson and Landreth, 2006;Block et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia

Milton¹,

Abeti²,

Averaimo³

et al. 2008

J. Neurosci.

128

131

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The Alzheimer's disease (AD) brain is characterized by plaques containing ␤-amyloid (A␤) protein surrounded by astrocytes and reactive microglia. Activation of microglia by A␤ initiates production of reactive oxygen species (ROS) by the plasmalemmal NADPH oxidase; the resultant oxidative stress is thought to contribute to neurodegeneration in AD. We have previously shown that A␤ upregulates a chloride current mediated by the chloride intracellular channel 1 (CLIC1) protein in microglia. We now demonstrate that A␤ promotes the acute translocation of CLIC1 from the cytosol to the plasma membrane of microglia, where it mediates a chloride conductance. Both the A␤ induced Cl Ϫ conductance and ROS generation were prevented by pharmacological inhibition of CLIC1, by replacement of chloride with impermeant anions, by an anti-CLIC1 antibody and by suppression of CLIC1 expression using siRNA. Thus, the CLIC1-mediated Cl Ϫ conductance is required for A␤-induced generation of neurotoxic ROS by microglia. Remarkably, CLIC1 activation is itself dependent on oxidation by ROS derived from the activated NADPH oxidase. We therefore propose that CLIC1 translocation from the cytosol to the plasma membrane, in response to redox modulation by NADPH oxidase-derived ROS, provides a feedforward mechanism that facilitates sustained microglial ROS generation by the NAPDH oxidase.

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Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with β-amyloid[25–35]

Cited by 141 publications

References 39 publications

Amyloid β-Induced Death in Neurons Involves Glial and Neuronal Hemichannels

Amyloid β-Induced Death in Neurons Involves Glial and Neuronal Hemichannels

Regulating Factors for Microglial Activation.

CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia

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