Curcumin ameliorates neuropathic pain by down-regulating spinal IL-1β via suppressing astroglial NALP1 inflammasome and JAK2-STAT3 signalling
| Autor: | Lang-Yue Hu, Wen-Li Mi, Gen-Cheng Wu, Shen-Bin Liu, Qian Li, Qi-Liang Mao-Ying, Yan-Qing Wang, Meng-Ting Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male STAT3 Transcription Factor Curcumin Inflammasomes Interleukin-1beta Down-Regulation Pharmacology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals STAT3 Adaptor Proteins Signal Transducing Mice Inbred BALB C Multidisciplinary Janus kinase 2 biology Activator (genetics) business.industry Inflammasome Janus Kinase 2 030104 developmental biology Allodynia chemistry Spinal Cord Hyperalgesia Neuropathic pain Immunology biology.protein Neuralgia medicine.symptom business Apoptosis Regulatory Proteins 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep28956 |
| Popis: | Curcumin has been shown to possess strong anti-inflammatory activity in many diseases. It has been demonstrated that the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade and the NAcht leucine-rich-repeat protein 1 (NALP1) inflammasome are important for the synthesis of Pro-Interleukin (IL)-1β and the processing of the inactive protein to its mature form, which plays an active role in the pathogenesis of neuropathic pain. The present study showed that repeated intraperitoneal injection of curcumin ameliorated SNI-induced mechanical and cold allodynia in a dose-dependent manner and inhibited the elevation of spinal mature IL-1β protein levels. Additionally, repeated curcumin treatment significantly inhibited the aggregation of the NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in spinal astrocytes. Furthermore, the genetic down-regulation of NALP1 inflammasome activation by NALP1 siRNA and the pharmacological inhibition of the JAK2-STAT3 cascade by AG490 markedly inhibited IL-1β maturation and Pro-IL-1β synthesis, respectively and reduced SNI-induced pain hypersensitivity. Our results suggest that curcumin attenuated neuropathic pain and down-regulated the production of spinal mature IL-1β by inhibiting the aggregation of NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in astrocytes. |
| Databáze: | OpenAIRE |
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