| First Author | Liu J | Year | 2007 |
| Journal | J Exp Med | Volume | 204 |
| Issue | 1 | Pages | 141-52 |
| PubMed ID | 17227910 | Mgi Jnum | J:125292 |
| Mgi Id | MGI:3758134 | Doi | 10.1084/jem.20061440 |
| Citation | Liu J, et al. (2007) Regulation of IL-27 p28 gene expression in macrophages through MyD88- and interferon-gamma-mediated pathways. J Exp Med 204(1):141-52 |
| abstractText | Interleukin (IL)-27 is the newest member of the IL-12 family of heterodimeric cytokines composed of the Epstein-Barr virus-induced gene 3 and p28 chains. IL-27 not only plays an important role in the regulation of differentiation of naive T helper cells but also possesses antiinflammatory properties. IL-27 is an early product of activated monocytes/macrophages and dendritic cells. However, the mechanisms whereby inflammatory signals stimulate IL-27 production have not been explored. In this study, we investigated the transcriptional regulation of the mouse IL-27 p28 gene in macrophages in response to lipopolysaccharide (LPS) and interferon (IFN)-gamma. We found that LPS-stimulated p28 production was completely dependent on the Toll-like receptor 4/myeloid differentiation factor 88 (MyD88)-mediated pathway but only partially dependent on nuclear factor kappaB c-Rel. IFN-gamma-induced p28 production/secretion was also partially dependent on MyD88 but independent of c-Rel. We then cloned the mouse p28 gene promoter and mapped its multiple transcription initiation sites. Furthermore, we identified critical promoter elements that mediate the inductive effects of LPS and IFN-gamma, separately and synergistically, on p28 gene transcription in a c-Rel- and interferon regulatory factor 1-dependent manner, respectively. |
