Redundancy of C/EBP alpha, -beta, and -delta in supporting the lipopolysaccharide-induced transcription of IL-6 and monocyte chemoattractant protein-1.
C/EBP alpha, -beta, and -delta 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/EBP beta and -delta increased by treatment with LPS while that of C/EBP alpha 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/EBP alpha, -beta, and -delta are redundant in regard to the expression of IL-6 and monocyte chemoattractant protein-1. Since C/EBP beta-deficient mice have been reported to be largely normal in their expression of proinflammatory cytokines, it is likely that the lack of C/EBP beta is compensated for by the induction of C/EBP delta upon LPS treatment.
Hu
H M
HM
Department of Microbiology, Michigan State University, East Lansing 48824, USA.
Baer
M
M
Williams
S C
SC
Johnson
P F
PF
Schwartz
R C
RC
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D007941:Leukemia P388 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
D000276:Adjuvants, Immunologic; D022762:CCAAT-Enhancer-Binding Proteins; D018932:Chemokine CCL2; D016207:Cytokines; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009687:Nuclear Proteins