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

Hsien-Ming Hu, Qiang Tian, Mark Baer, Chauncey J. Spooner, Simon C. Williams, Peter F. Johnson, Richard C. Schwartz
2000 Journal of Biological Chemistry  
C/EBP␣, ␤, and ␦ are all expressed by bone marrowderived 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/EBP␣, ␤, and ␦ are redundant in regard to expression of IL-6 and MCP-1.
more » ... risingly, the bZIP region of C/EBP␤, 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/EBP␤, C/EBP␦, and, to a lesser extent, C/EBP␣ 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/EBP␤ bZIP region to activate the IL-6 promoter in transient transfections is completely dependent upon an intact NF-B-binding site, supporting a model where the bZIP protein primarily functions to augment the activity of NF-B. Replacement of the leucine zipper of C/EBP␤ 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. CCAAT/enhancer-binding protein (C/EBP) 1 ␣, ␤, and ␦ are
doi:10.1074/jbc.m910269199 pmid:10748205 fatcat:ymyr55zvhja5nbfccn65epsfmu