Details

Autor(en) / Beteiligte

• Hu, Hsien-Ming
• Tian, Qiang
• Baer, Mark
• Spooner, Chauncey J.
• Williams, Simon C.
• Johnson, Peter F.
• Schwartz, Richard C.

Titel

The C/EBP bZIP Domain Can Mediate Lipopolysaccharide Induction of the Proinflammatory Cytokines Interleukin-6 and Monocyte Chemoattractant Protein-1

Ist Teil von

• The Journal of biological chemistry, 2000-05, Vol.275 (21), p.16373-16381

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2000

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• C/EBPα, β, and δ are all expressed by bone marrow-derived macrophages. Ectopic expression of any of these transcription factors is sufficient to confer lipopolysaccharide (LPS)-inducible expression of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) to a B lymphoblast cell line, which normally lacks C/EBP factors and does not display LPS induction of proinflammatory cytokines. Thus, the activities of C/EBPα, β, and δ are redundant in regard to expression of IL-6 and MCP-1. Surprisingly, the bZIP region of C/EBPβ, which lacks any previously described activation domains, can also confer LPS-inducible expression of IL-6 and MCP-1 in stable transfectants. Transient transfections reveal that the bZIP regions of C/EBPβ, C/EBPδ, and, to a lesser extent, C/EBPα can activate the IL-6 promoter and augment its induction by LPS. Furthermore, the transdominant inhibitor, LIP, can activate expression from the IL-6 promoter. The ability of the C/EBPβ bZIP region to activate the IL-6 promoter in transient transfections is completely dependent upon an intact NF-κB-binding site, supporting a model where the bZIP protein primarily functions to augment the activity of NF-κB. Replacement of the leucine zipper of C/EBPβ with that of GCN4 yields a chimeric protein that can dimerize and specifically bind to a C/EBP consensus sequence, but shows a markedly reduced ability to activate IL-6 and MCP-1 expression. These results implicate the leucine zipper domain in some function other than dimerization with known C/EBP family members, and suggest that C/EBP redundancy in regulating cytokine expression may result from their highly related bZIP regions.