Redundancy of C/EBPα, -β, and -δ in Supporting the Lipopolysaccharide-Induced Transcription of IL-6 and Monocyte Chemoattractant Protein-1

Abstract

AbstractC/EBPα, -β, and -δ are members of the CCAAT/enhancer binding protein family of transcriptional regulators. All three of these factors are expressed by bone marrow-derived macrophages, with the DNA binding activity of C/EBPβ and -δ increased by treatment with LPS while that of C/EBPα is decreased. We have ectopically expressed each C/EBP protein in P388 lymphoblasts. The expression of any of these transcription factors is sufficient to confer the LPS-inducible expression of IL-6 and monocyte chemoattractant protein-1 to lymphoblasts, which normally lack C/EBP factors and do not display LPS induction of proinflammatory cytokines. Thus, the activities of C/EBPα, -β, and -δ are redundant in regard to the expression of IL-6 and monocyte chemoattractant protein-1. Since C/EBPβ-deficient mice have been reported to be largely normal in their expression of proinflammatory cytokines, it is likely that the lack of C/EBPβ is compensated for by the induction of C/EBPδ upon LPS treatment.