ICNC Abstracts, ICNC 2018

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Up-regulation of HMGB1-TLR4 Inflammatory Pathway in Focal Cortical Dysplasia Type II
Ye Wu

Last modified: 2018-09-09

Abstract


Object We attempted to determine whether the inflammatory pathway HMGB1-TLR4 and the downstream proinflammatory cytokines is up-regulated in focal cortical dysplasia (FCD) type II.

Methods FCD type II and peri-FCD paired tissues from eight children with refractory epilepsy were collected. We examined the differences between FCD and peri-FCD tissues with respect to mRNA expression, protein, and protein interaction in HMGB1-TLR4 pathway biomarker and downstream pro-inflammatory factors in whole brain tissue. Then we tested intracellular distribution of HMGB1-TLR4 pathway biomarker in neurons, astrocytes, and oligodendrocytes respectively.

Results The protein expression levels of TLR4, cytoplasm HMGB1, TLR4/MyD88 complex, ubiquitination of TRAF6, p-IKK-β, p-IκB-α, p-NF-κB p65 and IL-1β, TNF-α in lesion tissues were significantly higher than peri-FCD controls. Total mRNA expression levels of TLR4, IL-1β, and TNF-α in lesion tissues were significantly higher, but HMGB1 had no significant change in FCD. In neurons and astrocytes inside FCD, the expression of TLR4 protein was significantly higher than that in peri-FCD tissues, and HMGB1 was mainly expressed in the cytoplasm, while expressed in the nuclei in peri-FCD tissues. Whereas in oligodendrocytes, there was no up-regulation of HMGB1-TLR4 pathway. We did not identify the correlation between the level of TLR4 activation and disease duration or frequency of epileptic seizures.

Conclusion  HMGB1-TLR4 pathway was up-regulated in the neurons and astrocytes inside FCD type II lesions, which led to an increase in the release of downstream proinflammatory cytokines. Correlation between the level of TLR4 activation and duration or frequency of epileptic seizures was not identified.

Keywords


HMGB1-TLR4; up-regulation; inflammation; FCD type II; neurons; astrocytes

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