Endogenous CD28 expressed on myeloma cells up-regulates interleukin-8 production: implications for multiple myeloma progression

Blood. 2001 Jul 1;98(1):187-93. doi: 10.1182/blood.v98.1.187.

Abstract

CD28 is the major costimulatory molecule on T cells. CD28 activation, in conjunction with T-cell receptor engagement, up-regulates transcription of several cytokines, including interleukin-2 (IL-2), through transcriptional activation of the RE/AP composite element. Although CD28 is not normally expressed on B cells or plasma cells, more than 90% of extramedullary myelomas (a late stage B-cell neoplasm) express CD28. The functional significance of this is unknown. The results of this study demonstrate that CD28 stimulates transcriptional activation of RE/AP-based reporters in B cells and myeloma cells. However, CD28 stimulation does not up-regulate IL-2 production in myeloma cell lines, demonstrating that the IL-2 promoter may not be a relevant RE/AP-containing target of CD28 in myelomas. Instead, an RE/AP composite element has been identified within the promoter of the IL-8 gene, a chemokine that promotes angiogenesis. Furthermore, stimulation of endogenous CD28 expressed by 3 myeloma cell lines increased IL-8 production. Therefore, the study demonstrates that CD28 is functional in myelomas to up-regulate transcription of endogenous genes, including IL-8. The proposal is made that aberrant expression of CD28 may play a role in the progression of multiple myeloma.

MeSH terms

  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • CD28 Antigens / metabolism*
  • CD28 Antigens / pharmacology*
  • Disease Progression
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • Mice
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Promoter Regions, Genetic / drug effects
  • Signal Transduction
  • Transcriptional Activation / drug effects
  • Transfection
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects*

Substances

  • CD28 Antigens
  • Interleukin-2
  • Interleukin-8