Suppression of TLR4/MyD88/TAK1/NF-κB/COX-2 Signaling Pathway in the Central Nervous System by Bexarotene, a Selective RXR Agonist, Prevents Hyperalgesia in the Lipopolysaccharide-Induced Pain Mouse Model
| Autor: | Meryem Temiz-Resitoglu, Seyhan Sahan-Firat, Sefika Pinar Senol, Demet Sinem Guden, Ayse Nihal Sari, Bahar Tunctan |
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| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Agonist medicine.drug_class Anti-Inflammatory Agents Pharmacology Biochemistry Neuroprotection 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine medicine Animals Hot plate test Bexarotene Analgesics Mice Inbred BALB C NF-kappa B p50 Subunit NF-κB General Medicine MAP Kinase Kinase Kinases Toll-Like Receptor 4 Retinoid X Receptors 030104 developmental biology chemistry Cyclooxygenase 2 Hyperalgesia Myeloid Differentiation Factor 88 TLR4 Signal transduction medicine.symptom 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Neurochemical Research. 46:624-637 |
| ISSN: | 1573-6903 0364-3190 |
| Popis: | A selective RXR agonist, bexarotene, has been shown to have anti-inflammatory, anti-nociceptive, and neuroprotective effects in several models of numerous neurological diseases characterized by systemic inflammation. The mechanisms underlying these effects remains unknown. To elucidate these mechanisms, we investigated whether the TLR4/MyD88/TAK1/NF-κB/COX-2 signaling pathway in the CNS mediates the effect of bexarotene to prevent hyperalgesia in the LPS-induced inflammatory pain mouse model. The reaction time to thermal stimuli within 30 s was evaluated by the hot plate test in male mice treated with saline, LPS (10 mg/kg), DMSO, and/or bexarotene (0.1, 1, 3, or 10 mg/kg) after 6 h. The latency to the thermal stimulus (18.11 ± 1.36 s) in the LPS-treated mice was significantly decreased by 30% compared with saline-treated mice (25.84 ± 1.99 s). Treatment with bexarotene only at a dose of 10 mg/kg showed a significant increase in the latency by 22.49 ± 1.00 s compared with LPS-treated mice. Bexarotene also prevented the reduction in RXRα protein expression associated with a rise in the expression of TLR4, MyD88, phosphorylated TAK1, NF-κB p65, phosphorylated NF-κB p65, COX-2, and IL-1β proteins, in addition to COX-2 activity and levels of PGE2 and IL-1β in the brains and spinal cords of the LPS-treated animals. Likely, decreased activity of TLR4/MyD88/TAK1/NF-κB/COX-2 signaling pathway in addition to increased pro-inflammatory cytokine formation in the CNS of mice participates in the protective effect of bexarotene against hyperalgesia induced by LPS. |
| Databáze: | OpenAIRE |
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