| First Author | Nerlich A | Year | 2015 |
| Journal | Biochim Biophys Acta | Volume | 1849 |
| Issue | 8 | Pages | 966-78 |
| PubMed ID | 26066982 | Mgi Jnum | J:233925 |
| Mgi Id | MGI:5788382 | Doi | 10.1016/j.bbagrm.2015.06.002 |
| Citation | Nerlich A, et al. (2015) C/EBPbeta is a transcriptional key regulator of IL-36alpha in murine macrophages. Biochim Biophys Acta 1849(8):966-78 |
| abstractText | Interleukin (IL)-36alpha - one of the novel members of the IL-1 family of cytokines - is a potent regulator of dendritic and T cells and plays an important role in inflammatory processes like experimental skin inflammation in mice and in mouse models for human psoriasis. Here, we demonstrate that C/EBPbeta, a transcription factor required for the selective expression of inflammatory genes, is a key activator of the Il36A gene in murine macrophages. RNAi-mediated suppression of C/EBPbeta expression in macrophages (C/EBPbeta(low) cells) significantly impaired Il36A gene induction following challenge with LPS. Despite the presence of five predicted C/EBP binding sites, luciferase reporter assays demonstrated that C/EBPbeta confers responsiveness to LPS primarily through a half-CRE*C/EBP element in the proximal Il36A promoter. Electrophoretic mobility shift assays showed that C/EBPbeta but not CREB proteins interact with this critical half-CRE*C/EBP element. In addition, overexpression of C/EBPbeta in C/EBPbeta(low) cells enhanced the expression of Il36A whereas CREB-1 had no effect. Finally, chromatin immunoprecipitation confirmed that C/EBPbeta but neither CREB-1, ATF-2 nor ATF4 is directly recruited to the proximal promoter region of the Il36A gene. Together, these findings demonstrate an essential role of C/EBPbeta in the regulation of the Il36A gene via the proximal half-CRE*C/EBP element in response to inflammatory stimuli. |
