Eukaryotic Translation Initiation Factor-6 Enhances Histamine and IL-2 Production in Mast Cells

• Published in: The Journal of immunology (1950) Vol. 166; no. 5; pp. 3606 - 3611
• Main Authors: Oh, Chad K, Filler, Scott G, Cho, Seong H
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.03.2001
• Subjects: Animals; Cell Line; Cycloheximide - pharmacology; Cyclosporine - pharmacology; Dexamethasone - pharmacology; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Genetic Vectors - biosynthesis; Green Fluorescent Proteins; Histamine - biosynthesis; Histamine Release - genetics; Histamine Release - immunology; Humans; Immunosuppressive Agents - pharmacology; Interleukin-2 - biosynthesis; Interleukin-2 - metabolism; Interleukin-4 - metabolism; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Mast Cells - drug effects; Mast Cells - immunology; Mast Cells - metabolism; Mice; Peptide Initiation Factors - biosynthesis; Peptide Initiation Factors - genetics; Peptide Initiation Factors - physiology; Receptors, IgE - physiology; RNA, Messenger - biosynthesis; Transfection; translation initiation factor 6; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.5.3606

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.