scholarly journals Electric Stimulation of Ear Reduces the Effect of Toll-Like Receptor 4 Signaling Pathway on Kainic Acid-Induced Epileptic Seizures in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
En-Tzu Liao ◽  
Yi-Wen Lin ◽  
Chun-Ping Huang ◽  
Nou-Ying Tang ◽  
Ching-Liang Hsieh
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Kainic Acid ◽  
Epileptic Seizure ◽  
Electric Stimulation ◽  
Epileptic Seizures ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Brain Areas

Epilepsy is a common clinical syndrome with recurrent neuronal discharges in the temporal lobe, cerebral cortex, and hippocampus. Clinical antiepileptic medicines are often ineffective or of little benefit in 30% of epileptic patients and usually cause severe side effects. Emerging evidence indicates the crucial role of inflammatory mediators in epilepsy. The current study investigates the role of toll-like receptor 4 (TLR4) and its underlying mechanisms in kainic acid- (KA-) induced epileptic seizures in rats. Experimental KA injection successfully initiated an epileptic seizure accompanied by increased expression of TLR4 in the prefrontal cortex, hippocampus, and somatosensory cortex. In addition, calcium-sensitive phosphorylated Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) increased after the initiation of the epileptic seizure. Furthermore, downstream-phosphorylated signal-regulated kinase (ERK), c-Jun NH2-terminal protein kinase (JNK), and p38 kinase simultaneously increased in these brain areas. Moreover, the transcriptional factor phosphorylated nuclear factor-κB (pNF-κB) increased, suggesting that nucleus transcription was affected. Furthermore, the aforementioned molecules decreased by an electric stimulation (ES) of either 2 Hz or 15 Hz of the ear in the three brain areas. Accordingly, we suggest that ES of the ear can successfully control epileptic seizures by regulating the TLR4 signaling pathway and has a therapeutic benefit in reducing epileptic seizures.

The role of Toll-like receptor 4 signaling pathway in ovarian, cervical, and endometrial cancers

Life Sciences ◽  
2020 ◽  
Vol 247 ◽  
pp. 117435 ◽  
Author(s):  
Luiz Antonio Lupi ◽  
Maira Smaniotto Cucielo ◽  
Henrique Spaulonci Silveira ◽  
Letícia Barbosa Gaiotte ◽  
Roberta Carvalho Cesário ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Endometrial Cancers

scholarly journals A Toll-Like Receptor-Responsive Kinase, Protein Kinase R, Is Inactivated in Endotoxin Tolerance through Differential K63/K48 Ubiquitination

mBio ◽  
2010 ◽  
Vol 1 (5) ◽  
Author(s):  
Darren J. Perkins ◽  
Nilofer Qureshi ◽  
Stefanie N. Vogel
Keyword(s):  
Protein Kinase ◽  
Systemic Infection ◽  
Endotoxin Tolerance ◽  
Toll Like Receptor ◽  
Protein Kinase R ◽  
Tlr Signaling ◽  
Toll Like Receptor 4 ◽  
Gram Negative ◽  
Kinetics Of

ABSTRACTOverwhelming inflammation triggered by systemic infection in bacterial sepsis contributes to the pathology of this condition. Toll-like receptors (TLRs) are important in early septic inflammation. As a safeguard, the innate immune system has evolved to counter excessive inflammation through the induction of “tolerance.” In endotoxin tolerance, TLR signaling is inhibited and/or attenuated by multiple mechanisms that mitigate the ability of lipopolysaccharide (LPS) to activate critical kinases through TLR4. Here, we describe a novel mechanism. Protein kinase R (PKR), a kinase normally activated by a subset of TLRs, is rendered unresponsive to LPS in endotoxin-tolerized cells. In its naive state, PKR is subject to K63-linked ubiquitination (Ub), followed by K48-linked Ub, in response to LPS. In tolerance, the kinetics of this differential Ub is altered, resulting in a predominance of K48-linked chains, concomitant with a loss of PKR activation. These findings provide a novel mechanism by which a TLR-responsive kinase may be rendered inactive in tolerance.IMPORTANCE“Endotoxin tolerance” is a period of transient unresponsiveness to the lipopolysaccharide (LPS) outer membrane component of Gram-negative bacteria that is induced by prior exposure to LPS through Toll-like receptor 4 (TLR4). The loss of LPS-inducible cytokine production by macrophages from patients who have experienced Gram-negative sepsis is well documented, and the increased susceptibility of such patients to reinfection has been attributed to the development of endotoxin tolerance. Multiple mechanisms have been proffered to account for this attenuated response. Using the LPS-responsive kinase protein kinase R (PKR), we have identified differential K48 versus K63 ubiquitination as an additional molecular mechanism by which signal-transducing elements may be inactivated in a state of endotoxin tolerance. This work is highly significant because it links recent discoveries concerning the important role of ubiquitination of signaling molecules in regulating TLR signaling with the loss of LPS responsiveness in tolerance.

Role of Toll like receptor 4 signaling pathway in the secondary damage induced by experimental spinal cord injury

Immunobiology ◽  
2015 ◽  
Vol 220 (9) ◽  
pp. 1039-1049 ◽  
Author(s):  
Daniela Impellizzeri ◽  
Akbar Ahmad ◽  
Rosanna Di Paola ◽  
Michela Campolo ◽  
Michele Navarra ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Experimental Spinal Cord Injury ◽  
Secondary Damage ◽  
Cord Injury
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