| First Author | Cao S | Year | 2006 |
| Journal | J Biol Chem | Volume | 281 |
| Issue | 36 | Pages | 26041-50 |
| PubMed ID | 16835236 | Mgi Jnum | J:117172 |
| Mgi Id | MGI:3695775 | Doi | 10.1074/jbc.M602222200 |
| Citation | Cao S, et al. (2006) NF-kappaB1 (p50) homodimers differentially regulate pro- and anti-inflammatory cytokines in macrophages. J Biol Chem 281(36):26041-50 |
| abstractText | NF-kappaB/Rel is a family of transcription factors whose activation has long been linked to the production of inflammatory cytokines. Here, we studied NF-kappaB signaling in the regulation of the anti-inflammatory cytokine, interleukin-10 (IL-10). We identified a role for a single NF-kappaB family member, NF-kappaB1 (p50), in promoting the transcription of IL-10. The NF-kappaB ciselement on IL-10 proximal promoter was located to -55/-46, where p50 can homodimerize and form a complex with the transcriptional co-activator CREB-binding protein to activate transcription. The other Rel family members appear to play a negligible role in IL-10 transcription. Mice lacking p50 were more susceptible to lethal endotoxemia, and macrophages taken from p50-/- mice exhibit skewed cytokine responses to lipopolysaccharide, characterized by decreased IL-10 and increased tumor necrosis factor and IL-12. Taken together, our studies demonstrate that NF-kappaB1 (p50) homodimers can be transcriptional activators of IL-10. The reciprocal regulation of pro- and anti-inflammatory cytokine production by NF-kappaB1 (p50) may provide potential new ways to manipulate the innate immune response. |
