title: Tumor necrosis factor alpha and interleukin-1 beta mRNA expression in HMC-1 cells: differential regulation of gene product expression by recombinant interleukin-4.
abstract: Cytokine-activation pathways in mast cells are supposed to play a significant role in host defense mechanisms and allergic reactions. Interleukin-4 (IL-4) is a well-characterized regulator of growth and function of mast cells. The human mast cell line HMC-1 was established from a patient suffering from mast cell leukemia and was shown to expose IL-4 binding sites. In the present study, the effects of recombinant human (rh) IL-4 and other rh cytokines (IL-2, IL-3, IL-6, IL-8) on expression of cytokine mRNA in HMC-1 cells were examined by Northern blot analysis using oligonucleotide probes. Tumor necrosis factor alpha (TNF-alpha) and IL-1 beta transcripts were found to be expressed constitutively in HMC-1 cells, whereas transcripts for IL-3, IL-4, IL-5, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) could not be detected. Of all cytokines tested, rhIL-4 was found to down-regulate IL-1 beta mRNA expression and formation of immunoreactive IL-1 beta protein in HMC-1 cells. The effect of IL-4 on IL-1 beta gene product expression was time- and dose-dependent (maximum effects obtained with 100 U/mL of rhIL-4). No effect of IL-4 on expression of TNF-alpha mRNA in HMC-1 cells was observed. These results raise the possibility that human mast cells are a source of both TNF-alpha and IL-1 beta. Furthermore, our study provides evidence that IL-4 regulates IL-1 beta gene product expression in HMC-1 cells. The HMC-1 cell line should be a useful tool for studying cytokine activation pathways in human mast cells.
authors.affiliation: Department of Internal Medicine I, University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Sillaber
authors.forename: D
authors.initials: D
authors.lastname: Bevec
authors.forename: J H
authors.initials: JH
authors.lastname: Butterfield
authors.forename: C
authors.initials: C
authors.lastname: Heppner
authors.forename: R
authors.initials: R
authors.lastname: Valenta
authors.forename: O
authors.initials: O
authors.lastname: Scheiner
authors.forename: D
authors.initials: D
authors.lastname: Kraft
authors.forename: K
authors.initials: K
authors.lastname: Lechner
authors.forename: P
authors.initials: P
authors.lastname: Bettelheim
authors.forename: P
authors.initials: P
authors.lastname: Valent
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015847:Interleukin-4 / Q000494:pharmacology; D007946:Leukemia, Mast-Cell; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4