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

Overview

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.

publication date

  • March 13, 1998

Research

keywords

  • B-Lymphocytes
  • Cell Transformation, Viral
  • DNA-Binding Proteins
  • Herpesvirus 4, Human
  • Interleukin-12
  • Macrophages
  • Repressor Proteins
  • Transcription Factors

Identity

Scopus Document Identifier

  • 0032513227

Digital Object Identifier (DOI)

  • 10.1074/jbc.273.11.6431

PubMed ID

  • 9497375

Additional Document Info

volume

  • 273

issue

  • 11