STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex
The medial prefrontal cortex (mPFC) is the main cortical area for processing both sensory and affective aspects of pain. Recently, mPFC was reported to participate in cancer-induced bone pain (CIBP) via the mechanism of central inflammation. STING is a key component of neuroinflammation in the centr...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/21/5188 |
| _version_ | 1797468855813013504 |
|---|---|
| author | Xiaoxuan Zhang Xin Li Wei Wang Yuxin Zhang Zhihao Gong Yuan Peng Jingxiang Wu Xingji You |
| author_facet | Xiaoxuan Zhang Xin Li Wei Wang Yuxin Zhang Zhihao Gong Yuan Peng Jingxiang Wu Xingji You |
| author_sort | Xiaoxuan Zhang |
| collection | DOAJ |
| description | The medial prefrontal cortex (mPFC) is the main cortical area for processing both sensory and affective aspects of pain. Recently, mPFC was reported to participate in cancer-induced bone pain (CIBP) via the mechanism of central inflammation. STING is a key component of neuroinflammation in the central neuron system by activating downstream TBK1 and NF-κB signaling pathways. We aimed to investigate whether STING regulated neuroinflammation in the mPFC in rat models of CIBP. It is worth noting that we found a significant upregulation of STING in the mPFC after CIBP, accompanied by activation of TBK1 and NF-κB signaling pathways. In addition, pain and anxiety-like behaviors were alleviated by intraperitoneal injection of the STING inhibitor C-176. Furthermore, in microglia GMI-R1 cells, C-176 reversed LPS-induced M1 polarization. Collectively, this evidence indicated that STING may contribute to cancer-induced bone pain by activating TBK1 and NF-κB, and by promoting M1 polarization of microglia in the mPFC. |
| first_indexed | 2024-03-09T19:13:16Z |
| format | Article |
| id | doaj.art-63cd7914a6c4444ca815b811ac0928ed |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T19:13:16Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-63cd7914a6c4444ca815b811ac0928ed2023-11-24T04:00:26ZengMDPI AGCancers2072-66942022-10-011421518810.3390/cancers14215188STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal CortexXiaoxuan Zhang0Xin Li1Wei Wang2Yuxin Zhang3Zhihao Gong4Yuan Peng5Jingxiang Wu6Xingji You7School of Medicine, Shanghai University, Shanghai 200444, ChinaSchool of Medicine, Shanghai University, Shanghai 200444, ChinaDepartment of Anesthesiology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Anesthesiology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Anesthesiology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Anesthesiology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Anesthesiology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaSchool of Medicine, Shanghai University, Shanghai 200444, ChinaThe medial prefrontal cortex (mPFC) is the main cortical area for processing both sensory and affective aspects of pain. Recently, mPFC was reported to participate in cancer-induced bone pain (CIBP) via the mechanism of central inflammation. STING is a key component of neuroinflammation in the central neuron system by activating downstream TBK1 and NF-κB signaling pathways. We aimed to investigate whether STING regulated neuroinflammation in the mPFC in rat models of CIBP. It is worth noting that we found a significant upregulation of STING in the mPFC after CIBP, accompanied by activation of TBK1 and NF-κB signaling pathways. In addition, pain and anxiety-like behaviors were alleviated by intraperitoneal injection of the STING inhibitor C-176. Furthermore, in microglia GMI-R1 cells, C-176 reversed LPS-induced M1 polarization. Collectively, this evidence indicated that STING may contribute to cancer-induced bone pain by activating TBK1 and NF-κB, and by promoting M1 polarization of microglia in the mPFC.https://www.mdpi.com/2072-6694/14/21/5188medial prefrontal cortexSTINGM1 microgliacancer-induced bone pain |
| spellingShingle | Xiaoxuan Zhang Xin Li Wei Wang Yuxin Zhang Zhihao Gong Yuan Peng Jingxiang Wu Xingji You STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex Cancers medial prefrontal cortex STING M1 microglia cancer-induced bone pain |
| title | STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
| title_full | STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
| title_fullStr | STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
| title_full_unstemmed | STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
| title_short | STING Contributes to Cancer-Induced Bone Pain by Promoting M1 Polarization of Microglia in the Medial Prefrontal Cortex |
| title_sort | sting contributes to cancer induced bone pain by promoting m1 polarization of microglia in the medial prefrontal cortex |
| topic | medial prefrontal cortex STING M1 microglia cancer-induced bone pain |
| url | https://www.mdpi.com/2072-6694/14/21/5188 |
| work_keys_str_mv | AT xiaoxuanzhang stingcontributestocancerinducedbonepainbypromotingm1polarizationofmicrogliainthemedialprefrontalcortex AT xinli stingcontributestocancerinducedbonepainbypromotingm1polarizationofmicrogliainthemedialprefrontalcortex AT weiwang stingcontributestocancerinducedbonepainbypromotingm1polarizationofmicrogliainthemedialprefrontalcortex AT yuxinzhang stingcontributestocancerinducedbonepainbypromotingm1polarizationofmicrogliainthemedialprefrontalcortex AT zhihaogong stingcontributestocancerinducedbonepainbypromotingm1polarizationofmicrogliainthemedialprefrontalcortex AT yuanpeng stingcontributestocancerinducedbonepainbypromotingm1polarizationofmicrogliainthemedialprefrontalcortex AT jingxiangwu stingcontributestocancerinducedbonepainbypromotingm1polarizationofmicrogliainthemedialprefrontalcortex AT xingjiyou stingcontributestocancerinducedbonepainbypromotingm1polarizationofmicrogliainthemedialprefrontalcortex |