Neuronal regulation of immune responses in the central nervous system

Tian, Li; Rauvala, Heikki; Gahmberg, Carl G.

doi:10.1016/j.it.2008.11.002

Cited by 116 publications

(103 citation statements)

References 97 publications

(158 reference statements)

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“…Monocytes cultured with HMGB1 release TNF-␣, IL-1, IL-6, IL-8, and macrophage inflammatory protein-1 but not anti-inflammatory cytokines, such as IL-10 and IL-12 (23,25). As such, HMGB1 has become a "necrotic marker" participating in the proinflammatory cascade of sec- ondary damage after spinal cord injury (18,42). In contrast to the failures of adult spinal cord regeneration in chicken and mammals, several vertebrates, including fish, amphibians, and reptiles, are capable of spontaneous regeneration following cord transection or tail amputation (38,78).…”

Section: Discussionmentioning

confidence: 99%

“…However, the mechanisms for these animals to circumvent secondary tissue damage by limiting the vicious self-propagating cycle of inflammation are still poorly understood. Given the evidence that mammalian HMGB1 mediates CNS inflammation (18,42), we speculate that the regenerative animals might share distinct HMGB1 regulatory mechanisms by limiting excessive inflammatory responses to facilitate spinal cord regeneration, i.e. either by differentially spatial-temporal regulation of two paralogs following injury or by alternative molecular signaling.…”

Section: Inflammatory Responses Elicited By Spinal Cord Injury (Sci)mentioning

confidence: 99%

“…Involvements of Intracellular gHMGB1 Two Paralogs in the Apoptosis of Neurons-HMGB1 was found to activate not only macrophages but also neurons (23,42). A plethora of studies have revealed that HMGB1 plays double-edged roles in neural development and neurodegeneration (59).…”

Section: Differential Responses Of Ghmgb1a and Ghmgb1b To The Spinal mentioning

confidence: 99%

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HMGB1 Protein Does Not Mediate the Inflammatory Response in Spontaneous Spinal Cord Regeneration

Dong

Huan

et al. 2013

Journal of Biological Chemistry

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Background: HMGB1 in spontaneously regenerating spinal cord does not trigger the inflammation in contrast to those in injured mammalian cords. Results: Gecko HMGB1 paralogs failed to interact with TLR2 and TLR4 but do with RAGE receptors to activate the signaling pathway. Conclusion: HMGB1 is beneficial for spontaneous spinal cord regeneration by eliciting negligible inflammation and promoting oligodendrocyte migration. Significance: HMGB1 displays distinct functions in regenerative vertebrates.

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Section: Discussionmentioning

confidence: 99%

Section: Inflammatory Responses Elicited By Spinal Cord Injury (Sci)mentioning

confidence: 99%

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HMGB1 Protein Does Not Mediate the Inflammatory Response in Spontaneous Spinal Cord Regeneration

Dong

Huan

et al. 2013

Journal of Biological Chemistry

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“…42,43 Thus, we determined the neuronal response to rotenone exposure in the presence of primary glia with or without MPO. Primary mesencephalic neuron-enriched cultures from WT mice were incubated with glial cells from Mpo Ϫ/Ϫ or WT mice using transwell chambers, after which the extent of neuronal cell death was determined using LDH analysis and CCK-8.…”

Section: Rotenone-triggered Neuronal Injury Is More Apparent In Co-cumentioning

confidence: 99%

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

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Rotenone exposure has emerged as an environmental risk factor for inflammation-associated neurodegenerative diseases. However, the underlying mechanisms responsible for the harmful effects of rotenone in the brain remain poorly understood. Herein, we report that myeloperoxidase (MPO) may have a potential regulatory role in rotenone-exposed brain-resident immune cells. We show that microglia, unlike neurons, do not undergo death; instead, they exhibit distinctive activated properties under rotenone-exposed conditions. Once activated by rotenone, microglia show increased production of reactive oxygen species, particularly HOCl. Notably, MPO, an HOClproducing enzyme that is undetectable under normal conditions, is significantly increased after exposure to rotenone. MPO-exposed glial cells also display characteristics of activated cells, producing proinflammatory cytokines and increasing their phagocytic activity. Interestingly, our studies with MPO inhibitors and MPO-knockout mice reveal that MPO deficiency potentiates, rather than inhibits, the rotenone-induced activated state of glia and promotes glial cell death. Furthermore, rotenone-triggered neuronal injury was more apparent in co-cultures with glial cells from Mpo ؊/؊ mice than in those from wildtype mice. Collectively, our data provide evidence that MPO has dual functionality under rotenone-exposed conditions, playing a critical regulatory role in modulating pathological and protective events in the brain.

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“…However, the adaptive immune response plays a role in stroke or TBI, when BBB might become permeable for T cells [44]. Neurons and astrocytes may upregulate toll-like receptors and release pro-inflammatory cytokines [45]. Consequently, there is a complex interplay of neurons, astrocytes, endothelial cells, microglia, and T cells.…”

Section: Introductionmentioning

confidence: 99%

Supportive or detrimental roles of P2Y receptors in brain pathology?—The two faces of P2Y receptors in stroke and neurodegeneration detected in neural cell and in animal model studies

Förster

Reiser

2015

Purinergic Signalling

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This review describing the role of P2Y receptors in neuropathological conditions focuses on obvious differences between results demonstrating either a role in neuroprotection or in neurodegeneration, depending on in vitro and in vivo models. Such critical juxtaposition puts special emphasis on discussions of beneficial and detrimental effects of P2Y receptor agonists and antagonists in these models. The mechanisms reported to underlie the protection in vitro include increased expression of oxidoreductase genes, like carbonyl reductase and thioredoxin reductase; increased expression of inhibitor of apoptosis protein-2; extracellular signal-regulated kinase-and Akt-mediated antiapoptotic signaling; increased expression of Bcl-2 proteins, neurotrophins, neuropeptides, and growth factors; decreased Bax expression; non-amyloidogenic APP shedding; and increased neurite outgrowth in neuronal cells. Animal studies investigating the influence of P2Y receptors in middle cerebral artery occlusion (MCAO) models for stroke prove beneficial effects of P2Y receptor antagonists. In MCAO mice and rats, the application of broad-range P2 receptor antagonists decreased the infarct volume and improved neurological outcome. Moreover, antagonists of the P2Y 1 receptor, one of the most abundant P2Y receptor subtypes in brain tissue, decreased neuronal loss and improved spatial memory in rats after traumatic brain injury (TBI). Currently available data show a discrepancy between in vitro and in vivo models concerning the benefits of P2Y receptor activation in pathological conditions. In vitro models demonstrate protection by P2Y receptor agonists, but in vivo P2Y receptor activation deteriorates the outcome after MCAO and controlled cortical impact brain injury, a TBI model. To broaden the scope of the review, we additionally discuss publications that demonstrate detrimental effects of P2Y receptor agonists in vitro and publications showing protective effects of agonists in vivo. All these studies help to better understand the significant role of P2Y receptors especially in stroke models and to develop pharmacological strategies for the treatment of stroke.

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Neuronal regulation of immune responses in the central nervous system

Cited by 116 publications

References 97 publications

HMGB1 Protein Does Not Mediate the Inflammatory Response in Spontaneous Spinal Cord Regeneration

HMGB1 Protein Does Not Mediate the Inflammatory Response in Spontaneous Spinal Cord Regeneration

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Supportive or detrimental roles of P2Y receptors in brain pathology?—The two faces of P2Y receptors in stroke and neurodegeneration detected in neural cell and in animal model studies

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