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)
Goto
M
M
Department of Laboratory Medicine, Kobe University School of Medicine, Japan.
Kumagai
S
S
Ryo
R
R
D015703:Antigens, CD / Q000097:blood*; D018952:Antigens, CD34; D014408:Biomarkers, Tumor / Q000276:immunology*; D002460:Cell Line; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis*; D016185:Receptors, Interleukin-3 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D015703:Antigens, CD; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D016185:Receptors, Interleukin-3; D014409:Tumor Necrosis Factor-alpha