Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-κB-mediated neuroinflammation in kainic acid-induced seizures

Shin, Hyun Joo; Kim, H; Heo, Rok Won; Choi, Wan Sung; Kwon, Hyug Moo; Roh, Gu Seob

doi:10.1038/cdd.2014.29

Cited by 24 publications

(33 citation statements)

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“…Several studies have suggested that TonEBP is involved in many inflammatory diseases, including rheumatoid arthritis, atherosclerosis, seizures, lipopolysaccharide-injected brain injury, and diabetes [15,27,28]. Here, we showed a role for TonEBP in TNF-a-induced hypothalamic inflammation and sickness responses.…”

Section: Discussionsupporting

confidence: 58%

Tonicity‐responsive enhancer binding protein (TonEBP) regulates TNF‐α‐induced hypothalamic inflammation

Kim

et al. 2019

FEBS Letters

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Tonicity‐responsive enhancer binding protein (TonEBP) is a widely expressed transcription factor and is important in the regulation of inflammatory cytokines. Here, we have identified TonEBP expression in the hypothalamus, which is particularly high in proopiomelanocortin (POMC) neurons. TonEBP overexpression stimulates POMC transcription, and TonEBP haploinsufficiency in TonEBP (+/−) mice results in a decrease in hypothalamic POMC expression. TonEBP (+/−) mice show reduced sickness responses, which include anorexia and hyperthermia, that are initially induced by tumor necrosis factor (TNF)‐α. TonEBP (+/−) mice also show lower levels of TNF‐α‐induced hypothalamic expression of POMC and pro‐inflammatory cytokines. These results suggest that TonEBP is an important molecular regulator in the development of inflammatory sickness responses through the control of POMC and pro‐inflammatory cytokine expression in the hypothalamus.

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Section: Discussionsupporting

confidence: 58%

Tonicity‐responsive enhancer binding protein (TonEBP) regulates TNF‐α‐induced hypothalamic inflammation

Kim

et al. 2019

FEBS Letters

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“…A recent study reported a tonicity-independent regulation of TonEBP in the brain in a rodent model of seizure induced by kainic acid (Shin et al, 2014). Notably, TonEBP expression was specifically elevated in the nuclei of neurons, but not in microglia.…”

Section: Discussionmentioning

confidence: 96%

“…1B). Expression of TonEBP in neurons and astrocytes has been reported in normal and kainic acidinduced lesioned brain (Maallem et al, 2006;Shin et al, 2014). Therefore, we examined if LPS induced any changes in the level or localization of TonEBP in neurons and astrocytes by double-labeling with either anti-NeuN or anti-GFAP antibodies and anti-TonEBP antibodies (Fig.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory signals induce the expression of tonicity-responsive enhancer binding protein (TonEBP) in microglia

Jeong

Bae

et al. 2016

Journal of Neuroimmunology

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Tonicity-responsive enhancer (TonE) binding protein (TonEBP) is known as an osmosensitive transcription factor that regulates cellular homeostasis during states of hypo- and hypertonic stress. In addition to its role in osmoadaptation, growing lines of evidence suggest that TonEBP might have tonicity-independent functions. In particular, a number of studies suggest that inflammatory stimuli induce the expression and activation of TonEBP in peripheral immune cells. However, whether TonEBP is expressed in microglia, resident immune cells of the central nervous system, is unknown. Here we show that inflammatory signals induce the expression of TonEBP in microglia both in vitro and in vitro. In cultured primary microglia, treatment with lipopolysaccharide (LPS), interferon-γ, and interleukin 4 increased the expression of TonEBP. Moreover, we found that stereotaxic injection of LPS into the substantia nigra region of rat brain increased TonEBP expression in OX-42-positive cells. Furthermore, expression of TonEBP was induced in OX-42-positive cells in a rat model of transient middle cerebral artery occlusion. Together these results show that the expression of TonEBP is regulated by inflammatory signals in mammalian brain, suggesting that TonEBP might play a part during neuroinflammation.

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“…It also influences dopaminergic neurotransmission [59] and the action of potential firing of superior cervical ganglion neurons by mediating SMIT1 and KCNQ2/3 [60]. In astrocytes, AQP4 and VEGF were directly regulated by NFAT5 [13, 61], which contributed to blood-brain barrier disruption and the infiltration of immune cells in kainic acid-induced seizures. On the other hand, NFAT5 protected astrocytes against ischemic damage via the SIRT1/Nrf2 pathway [33] and inhibited glioblastoma multiforme via the P13K/AKT pathway [62].…”

Section: The Function Of Nfat5mentioning

confidence: 99%

NFAT5 Has a Job in the Brain

Yang

Wang

Peng³

2018

Dev Neurosci

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Nuclear factor of activated T cells 5 (NFAT5) has recently been classified as a new member of the Rel family. In addition, there are 5 more well-defined members (NF-κB and NFAT1–4) in the Rel family, which participate in regulating the expression of immune and inflammatory response-related genes. NFAT5 was initially identified in renal medullary cells where it regulated the expression of osmoprotective-related genes during the osmotic response. Many studies have demonstrated that NFAT5 is highly expressed in the nuclei of neurons in fetal and adult brains. Additionally, its expression is approximately 10-fold higher in fetal brains. With the development of detection technologies (laser scanning confocal microscopy, transgene technology, etc.), recent studies suggest that NFAT5 is also expressed in glial cells and plays a more diverse functional role. This article aims to summarize the current knowledge regarding the expression of NFAT5, its regulation of activation, and varied biological functions in the brain.

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Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-κB-mediated neuroinflammation in kainic acid-induced seizures

Cited by 24 publications

References 50 publications

Tonicity‐responsive enhancer binding protein (TonEBP) regulates TNF‐α‐induced hypothalamic inflammation

Tonicity‐responsive enhancer binding protein (TonEBP) regulates TNF‐α‐induced hypothalamic inflammation

Inflammatory signals induce the expression of tonicity-responsive enhancer binding protein (TonEBP) in microglia

NFAT5 Has a Job in the Brain

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