| First Author | Hörber S | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 24 | Pages | 12851-61 |
| PubMed ID | 27129283 | Mgi Jnum | J:235017 |
| Mgi Id | MGI:5792624 | Doi | 10.1074/jbc.M116.718825 |
| Citation | Horber S, et al. (2016) The Atypical Inhibitor of NF-kappaB, IkappaBzeta, Controls Macrophage Interleukin-10 Expression. J Biol Chem 291(24):12851-61 |
| abstractText | Macrophages constitute a first line of pathogen defense by triggering a number of inflammatory responses and the secretion of various pro-inflammatory cytokines. Recently, we and others found that IkappaBzeta, an atypical IkappaB family member and transcriptional coactivator of selected NF-kappaB target genes, is essential for macrophage expression of a subset of pro-inflammatory cytokines, such as IL-6, IL-12, and CCL2. Despite defective pro-inflammatory cytokine expression, however, IkappaBzeta-deficient mice develop symptoms of chronic inflammation. To elucidate this discrepancy, we analyzed a regulatory role of IkappaBzeta for the expression of anti-inflammatory cytokines and identified IkappaBzeta as an essential activator of IL-10 expression. LPS-challenged peritoneal and bone marrow-derived macrophages from IkappaBzeta-deficient mice revealed strongly decreased transcription and secretion of IL-10 compared with wild-type mice. Moreover, ectopic expression of IkappaBzeta was sufficient to stimulate Il10 transcription. On the molecular level, IkappaBzeta directly activated the Il10 promoter at a proximal kappaB site and was required for the transcription-enhancing trimethylation of histone 3 at lysine 4. Together, our findings show for the first time the IkappaBzeta-dependent expression of an anti-inflammatory cytokine that is crucial in controlling immune responses. |
