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J Biol Chem. 2006 Sep 8;281(36):26041-50. Epub 2006 Jul 11.

NF-kappaB1 (p50) homodimers differentially regulate pro- and anti-inflammatory cytokines in macrophages.

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  • 1Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 20742, USA.


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.

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