Differential Neuroprotective Effects of Interleukin-1 Receptor Antagonist on Spinal Cord Neurons after Excitotoxic Injury

Schizas, Nikos; Perry, Sharn; Andersson, Bo; Wählby, Carolina; Kullander, Klas; Hailer, Nils P

doi:10.1159/000484607

Cited by 3 publications

(2 citation statements)

References 49 publications

(70 reference statements)

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“…The IL1RN protein is a strong antagonist of Il-1α and Il-1β, which are inducers of apoptosis in general, while Il-1β induces apoptosis specifically in neurons [84,85]. Furthermore, IL1RN was shown to protect neurons by inhibiting apoptosis due to various types of insults [86,87]. Another interesting finding was the reduction of the CDKN2A protein (Table S8).…”

Section: Discussionmentioning

confidence: 93%

Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation

Simchi

Panov

Morsy

et al. 2020

JCM

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The UBE3A gene codes for a protein with two known functions, a ubiquitin E3-ligase which catalyzes ubiquitin binding to substrate proteins and a steroid hormone receptor coactivator. UBE3A is most famous for its critical role in neuronal functioning. Lack of UBE3A protein expression leads to Angelman syndrome (AS), while its overexpression is associated with autism. In spite of extensive research, our understanding of UBE3A roles is still limited. We investigated the cellular and molecular effects of Ube3a deletion in mouse embryonic fibroblasts (MEFs) and Angelman syndrome (AS) mouse model hippocampi. Cell cultures of MEFs exhibited enhanced proliferation together with reduced apoptosis when Ube3a was deleted. These findings were supported by transcriptome and proteome analyses. Furthermore, transcriptome analyses revealed alterations in mitochondria-related genes. Moreover, an analysis of adult AS model mice hippocampi also found alterations in the expression of apoptosis- and proliferation-associated genes. Our findings emphasize the role UBE3A plays in regulating proliferation and apoptosis and sheds light into the possible effects UBE3A has on mitochondrial involvement in governing this balance.

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Section: Discussionmentioning

confidence: 93%

Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation

Simchi

Panov

Morsy

et al. 2020

JCM

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“…However, the precise mechanism underlying the anti-apoptotic effect of HGF remains unclear. As some pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) induce cell apoptosis [25,26,27], the anti-apoptotic effects of HGF may also be correlated with its anti-inflammatory activity (Figure 1).…”

Section: Neurotrophic Activities Of Hgf In Scimentioning

confidence: 99%

Multipotent Neurotrophic Effects of Hepatocyte Growth Factor in Spinal Cord Injury

Yamane

Misawa

Takigawa

et al. 2019

IJMS

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Spinal cord injury (SCI) results in neural tissue loss and so far untreatable functional impairment. In addition, at the initial injury site, inflammation induces secondary damage, and glial scar formation occurs to limit inflammation-mediated tissue damage. Consequently, it obstructs neural regeneration. Many studies have been conducted in the field of SCI; however, no satisfactory treatment has been established to date. Hepatocyte growth factor (HGF) is one of the neurotrophic growth factors and has been listed as a candidate medicine for SCI treatment. The highlighted effects of HGF on neural regeneration are associated with its anti-inflammatory and anti-fibrotic activities. Moreover, HGF exerts positive effects on transplanted stem cell differentiation into neurons. This paper reviews the mechanisms underlying the therapeutic effects of HGF in SCI recovery, and introduces recent advances in the clinical applications of HGF therapy.

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Intravenous transplantation of olfactory ensheathing cells reduces neuroinflammation after spinal cord injury via interleukin-1 receptor antagonist

et al. 2021

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Rationale: Olfactory ensheathing cell (OEC) transplantation has emerged as a promising therapy for spinal cord injury (SCI) repair. In the present study, we explored the possible mechanisms of OECs transplantation underlying neuroinflammation modulation. Methods: Spinal cord inflammation after intravenous OEC transplantation was detected in vivo and ex vivo by translocator protein PET tracer [ 18 F]F-DPA. To track transplanted cells, OECs were transduced with enhanced green fluorescent protein (eGFP) and HSV1-39tk using lentiviral vector and were monitored by fluorescence imaging and [ 18 F]FHBG study. Protein microarray analysis and ELISA studies were employed to analyze differential proteins in the injured spinal cord after OEC transplantation. The anti-inflammation function of the upregulated protein was also proved by in vitro gene knocking down experiments and OECs/microglia co-culture experiment. Results: The inflammation in the spinal cord was decreased after OEC intravenous transplantation. The HSV1-39tk-eGFP-transduced OECs showed no accumulation in major organs and were found at the injury site. After OEC transplantation, in the spinal cord tissues, the interleukin-1 receptor antagonist (IL-1Ra) was highly upregulated while many chemokines, including pro-inflammatory chemokines IL-1α, IL-1β were downregulated. In vitro studies confirmed that lipopolysaccharide (LPS) stimulus triggered OECs to secrete IL-1Ra. OECs significantly suppressed LPS-stimulated microglial activity, whereas IL-1Ra gene knockdown significantly reduced their ability to modulate microglial activity. Conclusion: The OECs that reached the lesion site were activated by the release of pro-inflammatory cytokines from activated microglia in the lesion site and secreted IL-1Ra to reduce neuroinflammation. Intravenous transplantation of OECs has high therapeutic effectiveness for the treatment of SCI via the secretion of IL-1Ra to reduce neuroinflammation.

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Differential Neuroprotective Effects of Interleukin-1 Receptor Antagonist on Spinal Cord Neurons after Excitotoxic Injury

Cited by 3 publications

References 49 publications

Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation

Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation

Multipotent Neurotrophic Effects of Hepatocyte Growth Factor in Spinal Cord Injury

Intravenous transplantation of olfactory ensheathing cells reduces neuroinflammation after spinal cord injury via interleukin-1 receptor antagonist

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