TUMOR-NECROSIS-FACTOR ALPHA-INDUCED UP-REGULATION OF INTERLEUKIN-3 RECEPTOR MESSENGER-RNA EXPRESSION IN A CD34-POSITIVE HEMATOPOIETIC-CELL LINE

Regulation of interleukin-3 receptor (IL-3R) gene expression by tumor necrosis factor alpha (TNF alpha) was investigated using an IL-3-depen dent CD34-positive hematopoietic cell line (KMT2) and a human megakary ocytic cell line (CMK). KMT2 expressed IL-3R alpha-subunit mRNA, where as the level of expression of IL-3R beta-subunit mRNA was low. CMK exp ressed IL-3R beta-subunit mRNA more strongly. The expression of IL-3R mRNA varied in the progenitor cells of different lineages, TNF alpha m arkedly enhanced expression of IL-3R beta-subunit mRNA in KMT2, wherea s it only slightly augmented IL-3R alpha-subunit mRNA level. TNF alpha weakly augmented IL-3R mRNAs in CMK. However, the enhancement of IL-3 R beta-subunit mRNA in CMK was hardly detectable. The effects of TNF a lpha on IL-3R mRNA expression were completely different in a primitive and in a more committed hematopoietic cell line. Addition of TNF alph a to KMT2 resulted in increased numbers of IL-3R on the cell surface w ithout increased IL-3R affinity. The combination of IL-3 with TNF alph a abolished TNF alpha-induced inhibition of proliferation of KMT2. The se results indicate that TNF alpha modulates the IL-3-responsiveness o f primitive hematopoietic cells through up-regulation of the expressio n of IL-3R mRNAs, especially that of IL-3R beta-subunit mRNA. Phorbol ester (TPA) enhanced the IL-3R mRNA expression in KMT2. TPA had little effect on induction of IL-3R beta-subunit mRNA expression, thus sugge sting that the activation of protein kinase C does not play a crucial role in TNF alpha-induced regulation of IL-3R mRNA expression.