Tumor necrosis factor alpha-induced up-regulation of interleukin-3 receptor mRNA 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-dependent CD34-positive hematopoietic cell line (KMT2) and a human megakaryocytic cell line (CMK). KMT2 expressed IL-3R alpha-subunit mRNA, whereas the level of expression of IL-3R beta-subunit mRNA was low. CMK expressed IL-3R beta-subunit mRNA more strongly. The expression of IL-3R mRNA varied in the progenitor cells of different lineages. TNF alpha markedly enhanced expression of IL-3R beta-subunit mRNA in KMT2, whereas it only slightly augmented IL-3R alpha-subunit mRNA level. TNF alpha weakly augmented IL-3R mRNAs in CMK. However, the enhancement of IL-3R beta-subunit mRNA in CMK was hardly detectable. The effects of TNF alpha on IL-3R mRNA expression were completely different in a primitive and in a more committed hematopoietic cell line. Addition of TNF alpha to KMT2 resulted in increased numbers of IL-3R on the cell surface without increased IL-3R affinity. The combination of IL-3 with TNF alpha abolished TNF alpha-induced inhibition of proliferation of KMT2. These results indicate that TNF alpha modulates the IL-3-responsiveness of primitive hematopoietic cells through up-regulation of the expression of IL-3R mRNAs, especially that of IL-3R beta-subunit mRNA. Phorbol ester (TPA) enhanced the IL-3R mRNA expression in KMT2.(ABSTRACT TRUNCATED AT 250 WORDS)