Eukaryotic translation initiation factor-6 enhances histamine and IL-2 production in mast cells.
Eukaryotic translation initiation factor (eIF)-6 is known to be important in ribosome biogenesis. Previously, we have discovered that eIF-6 mRNA is induced in lung in a murine model of asthma. We also found that there was enhanced eIF-6 expression in mast cells stimulated with PMA plus calcium ionophore. Therefore, we hypothesized that the induction of eIF-6 enhances the production of bioactive mediators by mast cells upon allergic stimulation. In the current study, we found that eIF-6 mRNA was rapidly induced in murine mast cells stimulated by Fc epsilon RI cross-linking, which is a major physiologic stimulant for mast cells. eIF-6 was also induced in human mast cells upon stimulation. The increase in eIF-6 gene expression in murine mast cells was blocked by therapeutic agents such as dexamethasone and cyclosporin A. To determine the location and function of eIF-6, murine mast cells were transfected with a construct that overexpressed enhanced green fluorescent protein-tagged eIF-6. These experiments demonstrated that eIF-6 was localized predominantly in the nucleolus of the mast cells. Also, overexpression of enhanced green fluorescent protein/eIF-6 enhanced the production of histamine and IL-2, but not IL-4 by stimulated murine mast cells. These results suggest that eIF-6 regulates the production of selected bioactive mediators in allergic diseases. This is the first demonstration of a biologic function of eIF-6 in mammalian cells.
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Division of Allergy and Immunology, Harbor-University of California, Los Angeles, Medical Center, Torrance, CA 90509, USA.
Filler
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Cho
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D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005822:Genetic Vectors / Q000096:biosynthesis; D049452:Green Fluorescent Proteins; D006632:Histamine / Q000096:biosynthesis*; D006636:Histamine Release / Q000235:genetics / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D010448:Peptide Initiation Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation / Q000276:immunology*
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D008164:Luminescent Proteins; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D017455:Receptors, IgE; C021019:eIF-6; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D003907:Dexamethasone; D006632:Histamine; D016572:Cyclosporine; D003513:Cycloheximide