TY - JOUR
T1 - Endogenous CD28 expressed on myeloma cells up-regulates interleukin-8 production
T2 - Implications for multiple myeloma progression
AU - Shapiro, Virginia Smith
AU - Mollenauer, Marianne Newton
AU - Weiss, Arthur
PY - 2001/7/1
Y1 - 2001/7/1
N2 - CD28 is the major costimulatory molecule on T cells. CD28 activation, in conjunction with T-cell receptor engagement, upregulates 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.
AB - CD28 is the major costimulatory molecule on T cells. CD28 activation, in conjunction with T-cell receptor engagement, upregulates 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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U2 - 10.1182/blood.V98.1.187
DO - 10.1182/blood.V98.1.187
M3 - Article
C2 - 11418479
AN - SCOPUS:0035412380
SN - 0006-4971
VL - 98
SP - 187
EP - 193
JO - Blood
JF - Blood
IS - 1
ER -