The TLR4 mediated inflammatory signal pathway might be involved in drug resistance in drug-resistant epileptic rats.

Xinghua Tang, Xiaoxia Chen, Xinjuan Li, Huan Cheng, Jing Gan, Zhenguo Liu

Journal of neuroimmunology 2022 Apr 15

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Background Recent data suggested that inflammatory responses are involved in the acute or chronic phase of drug-resistant epilepsy. The aim of this study was to examine the signal pathway of Toll-like receptors (TLR) 4 mediated drug resistance in refractory epileptic rats. Methods Lithium chloride and pilocarpine were used to establish a drug-resistant epilepsy rat model. Recombinant adenovirus was used to construct a TLR4 deficient drug-resistant epileptic rat model. The expression of TLR4, p-gp, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and nuclear factor kappa B (NF-κB) were determined by Western blot and Immunohistochemical analysis. Results P-gp, TLR4, NF-κB, IL-1β, TNF-α were significantly higher in the drug-resistant epileptic rats than in the epileptic rats (all P < 0.05). Contrary, this process was reversed in TLR4-deficient epileptic rats. The expression levels of P-gp, TLR4, NF-κB, IL-1β, and TNF-α expression were significantly inhibited in TLR4-deficient rats, suggesting that TLR4, as an important upstream factor, might significantly affect the expression levels of P-gp, NF-κB, IL-1β, and TNF-α (all P < 0.05). Conclusions Our study found the expression levels of TLR4, NF-κB, IL-1β, TNF-α which were related with inflammatory signal pathway changed in drug resistant epileptic rats. Our results suggest that TLR4, as an upstream regulator, could activate the downstream NF-κB, regulate inflammatory factors IL-1β, TNF-α, and other cytokines, and affect the expression level of P-gp in drug resistant epileptic rats. We speculate TLR4 related inflammatory signal pathway might take part in the emergence of epilepsy resistance, which is important in drug resistance. Copyright © 2021. Published by Elsevier B.V.

Citation

Xinghua Tang, Xiaoxia Chen, Xinjuan Li, Huan Cheng, Jing Gan, Zhenguo Liu. The TLR4 mediated inflammatory signal pathway might be involved in drug resistance in drug-resistant epileptic rats. Journal of neuroimmunology. 2022 Apr 15;365:577802