Endogenous CD28 expressed on myeloma cells up-regulates interleukin-8 production: implications for multiple myeloma progression.
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.
Shapiro
V S
VS
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA.
Mollenauer
M N
MN
Weiss
A
A
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism* / Q000494:pharmacology*; D018450:Disease Progression; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*
D018106:CD28 Antigens; D007376:Interleukin-2; D016209:Interleukin-8