Tiazofurin-induced autosecretion of IL-6 and hemoglobin production in K562 human leukemia cells.
Previous reports have established the synthesis of interleukin-6 (IL-6) and IL-6 receptors (IL-6R) in several human leukemia cells and found that IL-6 and the IL-6R could be expressed in cell lines with erythroid/megakaryocytic features. IL-6 is a pleiotropic cytokine involved in megakaryocytic differentiation. The finding that endogenous IL-6 levels in serum increased after 5-fluorouracil (5-FU) treatment suggests that IL-6 may play some role in the recovery of hematopoietic systems. This observation may assist the understanding of erythroid regeneration caused by antineoplastic agents such as tiazofurin. Tiazofurin inhibits the activity of IMP dehydrogenase. Its exposure to K562 cells at 10 microM tiazofurin stimulates erythroid differentiation. Stimulation of cells with tiazofurin gave a significant increase in IL-6 production. Its levels were quadrupled after 2 days of culture. Tiazofurin also caused a trivial reduction in the percentage of cells with the IL-6R. This evidence implies that tiazofurin produced no significant effect on the IL-6R. Tiazofurin also increased the percentage of benzidine-positive cells representing hemoglobin production, confirmed by GpA expression. We concluded that IL-6 is rate limiting in regard to hemoglobin production and that IL-3 could be used for clinical benefit to stimulate erythropoiesis and synergize with tiazofurin.
Talley
C J
CJ
Comprehensive Sickle Cell Center, Meharry Medical College, Nashville, Tennessee 37208, USA.
Turner
E A
EA
Hatcher
F M
FM
Aguinaga
P M
PM
Chakrabarti
P
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006454:Hemoglobins / Q000096:biosynthesis*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006454:Hemoglobins; D015850:Interleukin-6; D012254:Ribavirin; C033706:tiazofurin