The TLR4 mediated inflammatory signal pathway might be involved in drug resistance in drug-resistant epileptic rats.
J Neuroimmunol
; 365: 577802, 2022 04 15.
Article
en En
| MEDLINE
| ID: mdl-35217365
ABSTRACT
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)-1ß, 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-1ß, 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-1ß, 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-1ß, and TNF-α (all P < 0.05). Conclusions Our study found the expression levels of TLR4, NF-κB, IL-1ß, 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-1ß, 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
FN-kappa B
/
Epilepsia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Neuroimmunol
Año:
2022
Tipo del documento:
Article
País de afiliación:
China