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Blood, 1 July 2001, Vol. 98, No. 1, pp. 187-193
NEOPLASIA
Endogenous CD28 expressed on myeloma cells
up-regulates interleukin-8 production: implications for multiple
myeloma progression
Virginia Smith Shapiro,
Marianne Newton Mollenauer, and
Arthur Weiss
From the Department of Pathology and Laboratory
Medicine, University of Pennsylvania, Philadelphia, and the Department
of Medicine and Howard Hughes Medical Institute, University of
California, San Francisco.
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.
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