H M Hu

Publications (2)10.56 Total impact

• Article: The C/EBP bZIP domain can mediate lipopolysaccharide induction of the proinflammatory cytokines interleukin-6 and monocyte chemoattractant protein-1.

  H M Hu, Q Tian, M Baer, C J Spooner, S C Williams, P F Johnson, R C Schwartz
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  ABSTRACT: C/EBPalpha, beta, and delta 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/EBPalpha, beta, and delta are redundant in regard to expression of IL-6 and MCP-1. Surprisingly, the bZIP region of C/EBPbeta, 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/EBPbeta, C/EBPdelta, and, to a lesser extent, C/EBPalpha 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/EBPbeta bZIP region to activate the IL-6 promoter in transient transfections is completely dependent upon an intact NF-kappaB-binding site, supporting a model where the bZIP protein primarily functions to augment the activity of NF-kappaB. Replacement of the leucine zipper of C/EBPbeta 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.
  Journal of Biological Chemistry 06/2000; 275(21):16373-81. · 4.77 Impact Factor
• Article: Redundancy of C/EBP alpha, -beta, and -delta in supporting the lipopolysaccharide-induced transcription of IL-6 and monocyte chemoattractant protein-1.

  H M Hu, M Baer, S C Williams, P F Johnson, R C Schwartz
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  ABSTRACT: 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.
  The Journal of Immunology 03/1998; 160(5):2334-42. · 5.79 Impact Factor