High-Mobility Group Box-1 and Its Receptors Contribute to Proinflammatory Response in the Acute Phase of Spinal Cord Injury in Rats

Chen, Ke-Bing; Uchida, Kenzo; Nakajima, Hideaki; Yayama, Takafumi; Hirai, Takayuki; Guerrero, Alexander Rodríguez; Kobayashi, Shigeru; Ma, Wei-Ying; Liu, Shaoyu; Zhu, Ping; Baba, H.

doi:10.1097/brs.0b013e318203941c

Cited by 60 publications

(71 citation statements)

References 49 publications

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“…Extracellular HMGB1 acts as ligand and sensor for innate immunity to promote recruitments of inflammatory cells and to elicit release of inflammatory cytokines, thus initiating a vicious circle between injured neurons and uncontrolled inflammation (13,72,77). In traumatic spinal cord of rat, HMGB1 was significantly up-regulated from 6 h, acting on the roles of the release of TNF-␣, IL-1␤, and IL-6 (15,18). 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).…”

Section: Discussionmentioning

confidence: 98%

“…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%

“…HMGB1 also serves to induce neuroinflammation after injury, such as lesions in the spinal cord and brain (16,18,59). To elucidate whether neuron and microglia, a type of glial cells that are the resident macrophages of the brain and spinal cord, have participated in the physiological processes through activation of one or both HMGB1 paralog signalings, we first succeeded in preparation of the recombinant proteins by eukaryotic expression in 293T cells and then of the polyclonal antibodies (Fig.…”

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

confidence: 99%

“…In various CNS injury models, inhibition of HMGB1 has been shown to reduce the severity of the lesion and microglial activation (16,17). As such, HMGB1 has been proposed to be a significant proinflammatory cytokine mediating progressive spinal cord injury (15,18).…”

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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: 98%

Section: Discussionmentioning

confidence: 99%

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

confidence: 99%

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

confidence: 99%

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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High mobility group box-1 serves a pathogenic role in spinal cord injury via the promotion of pro-inflammatory cytokines

Chen

Chang

Wang

et al. 2021

Journal of Leukocyte Biology

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Traumatic spinal cord injury (SCI) is a devastating condition marked by permanent motor, sensory, and autonomic dysfunction, in which the inflammatory response serves an important and preventable role. High mobility group box‐1 (HMGB1) is a potent regulator of inflammation in numerous acute and chronic inflammatory conditions.; however, the role of HMGB1 in SCI remains unclear. The present study aimed to characterize the temporal dynamics of HMGB1 release after SCI, to investigate the role of spinal microglia activation in mediating the effects of HMGB1 on SCI, and to explore the therapeutic potential of intrathecal anti‐HMGB1 polyclonal antibody on alleviating SCI. The present study demonstrated that HMGB1 expression was increased immediately after traumatic injury of a primary spinal neuron culture. It was found that neutralizing HMGB1 significantly ameliorated SCI pathogenesis and hind limb paralysis. Moreover, the levels of a number of pro‐inflammatory cytokines in the SCI lesion were reduced when local HMGB1 was blocked by anti‐HMGB1 antibody. In addition, the injured neuron‐derived conditioned medium increased TNF‐α secretion and the NF‐κB pathway in the BV2 microglia cell line via HMGB1. Collectively, these results indicated that HMGB1 served an important role in SCI inflammation and suggested the therapeutic potential of an anti‐HMGB1 antibody for SCI.

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Spinal astrocytes stimulated by tumor necrosis factor‐α and/or interferon‐γ attenuate connexin 43‐gap junction via c‐jun terminal kinase activity

Zhang

Morioka

Nakashima-Hisaoka

et al. 2013

J of Neuroscience Research

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Spinal astrocytes have important mechanistic contributions to the initiation and maintenance of neurodegenerative diseases and chronic pain. Under inflammatory conditions, spinal astrocytes are exposed to cytokines such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and these cytokines could alter astrocytic function by modulating connexin (Cx43), subunits that form channels that modulate intercellular communication in astrocytes. The current study investigated the alteration of Cx43-gap junction in rat primary cultured spinal astrocytes stimulated with cytokines by real-time PCR and Western blotting. The transcriptional and translational levels of Cx43 were significantly but partially reduced 24 and 48 hr treatment with either TNF-α (10 ng/ml) or IFN-γ (5 ng/ml). A mixture of TNF-α and IFN-γ led to a robust decrease of Cx43 expression and, moreover, a moderate reduction of gap junction intercellular communication (GJIC), which was evaluated by a scrap loading/dye transfer assay. Both the decrease of Cx43 expression and the reduction in GJIC induced by the mixture of TNF-α and IFN-γ were prevented by blocking c-jun terminal kinase (JNK) but not by blocking extracellular signaling molecules ERK and p38 kinase, indicating a specific role of astrocytic JNK in the response to cytokines. In addition, treatment with cytokines potently induced the phosphorylation of JNK and c-jun in a time-dependent manner. These results indicate that intercellular communication of astrocytes is significantly disrupted in the inflammatory state and that stimulation of spinal astrocytes with inflammatory cytokines leads to significant inhibition of Cx43-GJIC through activation of the JNK signaling pathway.

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High-Mobility Group Box-1 and Its Receptors Contribute to Proinflammatory Response in the Acute Phase of Spinal Cord Injury in Rats

Cited by 60 publications

References 49 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

High mobility group box-1 serves a pathogenic role in spinal cord injury via the promotion of pro-inflammatory cytokines

Spinal astrocytes stimulated by tumor necrosis factor‐α and/or interferon‐γ attenuate connexin 43‐gap junction via c‐jun terminal kinase activity

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