TREM2 Regulates High Glucose-Induced Microglial Inflammation via the NLRP3 Signaling Pathway
<b>Background:</b> TREM2 expressed on microglia plays an important role in modulating inflammation in neurodegenerative diseases. It remains unknown whether TREM2 modulates hyperglycemia-induced microglial inflammation. <b>Methods:</b> We investigated the molecular function o...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/11/7/896 |
| _version_ | 1797527537719443456 |
|---|---|
| author | Yuan Li Weihong Long Menghan Gao Fangtai Jiao Zecai Chen Mingyuan Liu Lu Yu |
| author_facet | Yuan Li Weihong Long Menghan Gao Fangtai Jiao Zecai Chen Mingyuan Liu Lu Yu |
| author_sort | Yuan Li |
| collection | DOAJ |
| description | <b>Background:</b> TREM2 expressed on microglia plays an important role in modulating inflammation in neurodegenerative diseases. It remains unknown whether TREM2 modulates hyperglycemia-induced microglial inflammation. <b>Methods:</b> We investigated the molecular function of TREM2 in high glucose-induced microglial inflammation using western blotting, qPCR, ELISA, pulldown, and co-IP methods. <b>Results:</b> Our data showed that in high glucose-induced BV2 cells, TREM2 was increased, and the proinflammatory cytokine IL-1β was increased. TREM2 knockout (KO) attenuated the proinflammatory cytokine IL-1β; conversely, TREM2 overexpression (OE) exacerbated IL-1β expression. Furthermore, we found that high glucose promoted the interaction of TREM2 with NLRP3. TREM2 KO abolished the interaction of TREM2 with NLRP3, while TREM2 OE enhanced the interaction. Moreover, TREM2 KO reduced high glucose-induced NLRP3 inflammasome activation, and TREM2 OE augmented high glucose-induced NLRP3 inflammasome activation, indicating that high glucose enhances the expression of TREM2, which activates the NLRP3 inflammasome. To further clarify whether the NLRP3 signaling pathway mediates the TREM2-regulated inflammatory response, we blocked the NLRP3 inflammasome by knocking out NLRP3 and treating cells with a caspase1 inhibitor, which decreased the levels of the IL-1β proinflammatory cytokine but did not affect the high glucose-induced expression of TREM2. <b>Conclusions:</b> TREM2 modulates high glucose-induced microglial inflammation via the NLRP3 signaling pathway. |
| first_indexed | 2024-03-10T09:45:06Z |
| format | Article |
| id | doaj.art-7d7ce80842ee415a8f30abff313b906a |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-10T09:45:06Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-7d7ce80842ee415a8f30abff313b906a2023-11-22T03:20:19ZengMDPI AGBrain Sciences2076-34252021-07-0111789610.3390/brainsci11070896TREM2 Regulates High Glucose-Induced Microglial Inflammation via the NLRP3 Signaling PathwayYuan Li0Weihong Long1Menghan Gao2Fangtai Jiao3Zecai Chen4Mingyuan Liu5Lu Yu6Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine of Jilin University, Changchun 130000, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine of Jilin University, Changchun 130000, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine of Jilin University, Changchun 130000, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine of Jilin University, Changchun 130000, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine of Jilin University, Changchun 130000, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine of Jilin University, Changchun 130000, ChinaKey Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine of Jilin University, Changchun 130000, China<b>Background:</b> TREM2 expressed on microglia plays an important role in modulating inflammation in neurodegenerative diseases. It remains unknown whether TREM2 modulates hyperglycemia-induced microglial inflammation. <b>Methods:</b> We investigated the molecular function of TREM2 in high glucose-induced microglial inflammation using western blotting, qPCR, ELISA, pulldown, and co-IP methods. <b>Results:</b> Our data showed that in high glucose-induced BV2 cells, TREM2 was increased, and the proinflammatory cytokine IL-1β was increased. TREM2 knockout (KO) attenuated the proinflammatory cytokine IL-1β; conversely, TREM2 overexpression (OE) exacerbated IL-1β expression. Furthermore, we found that high glucose promoted the interaction of TREM2 with NLRP3. TREM2 KO abolished the interaction of TREM2 with NLRP3, while TREM2 OE enhanced the interaction. Moreover, TREM2 KO reduced high glucose-induced NLRP3 inflammasome activation, and TREM2 OE augmented high glucose-induced NLRP3 inflammasome activation, indicating that high glucose enhances the expression of TREM2, which activates the NLRP3 inflammasome. To further clarify whether the NLRP3 signaling pathway mediates the TREM2-regulated inflammatory response, we blocked the NLRP3 inflammasome by knocking out NLRP3 and treating cells with a caspase1 inhibitor, which decreased the levels of the IL-1β proinflammatory cytokine but did not affect the high glucose-induced expression of TREM2. <b>Conclusions:</b> TREM2 modulates high glucose-induced microglial inflammation via the NLRP3 signaling pathway.https://www.mdpi.com/2076-3425/11/7/896diabetesmicrogliaTREM2NLRP3 |
| spellingShingle | Yuan Li Weihong Long Menghan Gao Fangtai Jiao Zecai Chen Mingyuan Liu Lu Yu TREM2 Regulates High Glucose-Induced Microglial Inflammation via the NLRP3 Signaling Pathway Brain Sciences diabetes microglia TREM2 NLRP3 |
| title | TREM2 Regulates High Glucose-Induced Microglial Inflammation via the NLRP3 Signaling Pathway |
| title_full | TREM2 Regulates High Glucose-Induced Microglial Inflammation via the NLRP3 Signaling Pathway |
| title_fullStr | TREM2 Regulates High Glucose-Induced Microglial Inflammation via the NLRP3 Signaling Pathway |
| title_full_unstemmed | TREM2 Regulates High Glucose-Induced Microglial Inflammation via the NLRP3 Signaling Pathway |
| title_short | TREM2 Regulates High Glucose-Induced Microglial Inflammation via the NLRP3 Signaling Pathway |
| title_sort | trem2 regulates high glucose induced microglial inflammation via the nlrp3 signaling pathway |
| topic | diabetes microglia TREM2 NLRP3 |
| url | https://www.mdpi.com/2076-3425/11/7/896 |
| work_keys_str_mv | AT yuanli trem2regulateshighglucoseinducedmicroglialinflammationviathenlrp3signalingpathway AT weihonglong trem2regulateshighglucoseinducedmicroglialinflammationviathenlrp3signalingpathway AT menghangao trem2regulateshighglucoseinducedmicroglialinflammationviathenlrp3signalingpathway AT fangtaijiao trem2regulateshighglucoseinducedmicroglialinflammationviathenlrp3signalingpathway AT zecaichen trem2regulateshighglucoseinducedmicroglialinflammationviathenlrp3signalingpathway AT mingyuanliu trem2regulateshighglucoseinducedmicroglialinflammationviathenlrp3signalingpathway AT luyu trem2regulateshighglucoseinducedmicroglialinflammationviathenlrp3signalingpathway |