For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

Synergistic regulation of the human interleukin-12 p40 promoter by NFkappaB and Ets transcription factors in Epstein-Barr virus-transformed B cells and macrophages.

TitleSynergistic regulation of the human interleukin-12 p40 promoter by NFkappaB and Ets transcription factors in Epstein-Barr virus-transformed B cells and macrophages.
Publication TypeJournal Article
Year of Publication1998
AuthorsGri G, Savio D, Trinchieri G, Ma X
JournalJ Biol Chem
Volume273
Issue11
Pagination6431-8
Date Published1998 Mar 13
ISSN0021-9258
KeywordsB-Lymphocytes, Binding Sites, Cell Transformation, Viral, DNA-Binding Proteins, Gene Expression Regulation, Genes, Reporter, Herpesvirus 4, Human, Humans, Interleukin-12, Macrophages, NF-kappa B, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Protein c-ets-2, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-rel, Repressor Proteins, T-Lymphocytes, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation
Abstract

Monocytes/macrophages produce interleukin-12 (IL-12) in response to pathogenic stimulation, whereas most Epstein-Barr virus-transformed (EBV+) B cells constitutively secrete IL-12. The molecular mechanism regulating the constitutive IL-12 gene expression in EBV+ B cells has not been addressed. In this study, using the EBV+ B cell line RPMI-8866, we localized to the human IL-12 p40 promoter two essential cis elements, the NFkappaB site and the Ets site. The NFkappaB site was shown to interact with members of the NFkappaB family: p50 and c-Rel. The Ets site constitutively bound a multi-component Ets-2-containing complex. While the NFkappaB and Ets sites appear equally critical for inducible p40 promoter activity in macrophage cell lines, NFkappaB plays a more dominant role in the constitutive p40 promoter activity in EBV+ B cells. Transient expression of Ets-2 and c-Rel in B, T, and monocytic cell lines synergistically activated the IL-12 p40 promoter, apparently overcoming the requirement for cell type- or stimulant-specific transcription factors. These data provide new evidence that full activation of the human IL-12 p40 promoter may result primarily from the interplay between NFkappaB and Ets family members.

DOI10.1074/jbc.273.11.6431
Alternate JournalJ Biol Chem
PubMed ID9497375
Grant ListCA10815 / CA / NCI NIH HHS / United States
CA20833 / CA / NCI NIH HHS / United States
CA32898 / CA / NCI NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587