| First Author | Jeong GW | Year | 2020 |
| Journal | J Neuroinflammation | Volume | 17 |
| Issue | 1 | Pages | 372 |
| PubMed ID | 33292328 | Mgi Jnum | J:317143 |
| Mgi Id | MGI:6801226 | Doi | 10.1186/s12974-020-02007-9 |
| Citation | Jeong GW, et al. (2020) Microglial TonEBP mediates LPS-induced inflammation and memory loss as transcriptional cofactor for NF-kappaB and AP-1. J Neuroinflammation 17(1):372 |
| abstractText | BACKGROUND: Microglia are brain-resident myeloid cells involved in the innate immune response and a variety of neurodegenerative diseases. In macrophages, TonEBP is a transcriptional cofactor of NF-kappaB which stimulates the transcription of pro-inflammatory genes in response to LPS. Here, we examined the role of microglial TonEBP. METHODS: We used microglial cell line, BV2 cells. TonEBP was knocked down using lentiviral transduction of shRNA. In animals, TonEBP was deleted from myeloid cells using a line of mouse with floxed TonEBP. Cerulenin was used to block the NF-kappaB cofactor function of TonEBP. RESULTS: TonEBP deficiency blocked the LPS-induced expression of pro-inflammatory cytokines and enzymes in association with decreased activity of NF-kappaB in BV2 cells. We found that there was also a decreased activity of AP-1 and that TonEBP was a transcriptional cofactor of AP-1 as well as NF-kappaB. Interestingly, we found that myeloid-specific TonEBP deletion blocked the LPS-induced microglia activation and subsequent neuronal cell death and memory loss. Cerulenin disrupted the assembly of the TonEBP/NF-kappaB/AP-1/p300 complex and suppressed the LPS-induced microglial activation and the neuronal damages in animals. CONCLUSIONS: TonEBP is a key mediator of microglial activation and neuroinflammation relevant to neuronal damage. Cerulenin is an effective blocker of the TonEBP actions. |
