| First Author | Kanemaru H | Year | 2018 |
| Journal | Int Immunol | Volume | 30 |
| Issue | 6 | Pages | 255-265 |
| PubMed ID | 29534174 | Mgi Jnum | J:262227 |
| Mgi Id | MGI:6159190 | Doi | 10.1093/intimm/dxy023 |
| Citation | Kanemaru H, et al. (2018) BATF2 activates DUSP2 gene expression and up-regulates NF-kappaB activity via phospho-STAT3 dephosphorylation. Int Immunol 30(6):255-265 |
| abstractText | Growing evidence has revealed that the transcription factor basic leucine zipper transcription factor ATF-like 2 (BATF2) has unique transcriptional activities, including regulating cytokines via TLR signals in macrophages, which affect mortality due to infection and cancer. On the basis of genome-wide analyses using the chromatin immunoprecipitation-sequencing technique, we found that dual-specificity phosphatase 2 (Dusp2) had a significantly lower acetyl-histone status in Batf2-/- bone marrow-derived macrophages (BMDMs) compared with wild-type (WT) BMDMs. The phosphatase DUSP2 has been reported to play a critical role in inflammatory responses. Therefore, we evaluated the BATF2 transcriptional activities on the Dusp2 promoter. We found that the DUSP2 and IL-12 p40 expression levels were significantly lower in Batf2-/- BMDMs than in WT controls following their stimulation with TLR7 ligands. Further in vitro studies revealed that phospho-STAT3 was up-regulated and NF-kappaB p50/p65 were down-regulated in Batf2-/- BMDMs compared with their levels in WT controls. Additionally, Th1 immunity was impaired in Batf2-/- mice following their stimulation with TLR7 ligands. We also found that BATF2 interacts with NF-kappaB p65 and promotes DUSP2 expression through the NF-kappaB-binding site in the Dusp2 promoter at -203 to -121. Collectively, our findings suggest that BATF2 activates DUSP2 gene expression and up-regulates NF-kappaB activity via phospho-STAT3 dephosphorylation. |
