| First Author | Murphy TL | Year | 1995 |
| Journal | Mol Cell Biol | Volume | 15 |
| Issue | 10 | Pages | 5258-67 |
| PubMed ID | 7565674 | Mgi Jnum | J:28788 |
| Mgi Id | MGI:76327 | Doi | 10.1128/mcb.15.10.5258 |
| Citation | Murphy TL, et al. (1995) Regulation of interleukin 12 p40 expression through an NF-kappa B half-site. Mol Cell Biol 15(10):5258-67 |
| abstractText | Interleukin 12 (IL-12) is an inducible cytokine composed of 35- and 40-kDa subunits that is critical for promoting T helper type 1 development and cell-mediated immunity against pathogens. The 40-kDa subunit, expressed by activated macrophages and B cells, is induced by several pathogens in vivo and in vitro and is augmented or inhibited by gamma interferon (IFN-gamma) or IL-10, respectively. Control of IL-12 p40 expression is therefore important for understanding resistance and susceptibility to a variety of pathogens, including Leishmania major and perhaps human immunodeficiency virus. In this report, we provide the first characterization of IL-12 p40 gene regulation in macrophages. We localize inducible activity of the promoter to the sequence -122GGGGAATTTTA-132 not previously recognized to bind Rel family transcription factors. We demonstrate binding of this sequence to NF-kappa B (p50/p65 and p50/c-Rel) complexes in macrophages activated by several p40-inducing pathogens and provide functional data to support a role for NF-kappa B family members in IL-12 p40 activation. Finally, we find that IFN-gamma treatment of cells enhances this binding interaction, thus potentially providing a mechanism for IFN-gamma augmentation of IL-12 production by macrophages. |
