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 i n ribosome biogenesis, Previously, we have discovered that eIF-6 mRNA is in duced in lung in a murine model of asthma, T-Ve also found that there was e nhanced eIF-6 expression in mast cells stimulated with PMA plus calcium ion ophore, 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 muri ne mast cells stimulated by Fc epsilon RI cross-linking, which is a major p hysiologic stimulant for mast cells, eIF-6 was also induced in human mast c ells upon stimulation. The increase in eIF-6 gene expression in murine mast cells was blocked by therapeutic agents such as dexamethasone and cyclospo rin A. To determine the location and function of eIF-6, murine mast cells w ere transfected with a construct that overexpressed enhanced green fluoresc ent protein-tagged eIF-6, These experiments demonstrated that eIF-6 was loc alized predominantly in the nucleolus of the mast cells. Also, overexpressi on of enhanced green fluorescent protein/eIF-6 enhanced the production of h istamine and IL-2, but not IL-4 by stimulated murine mast cells. These resu lts suggest that eIF-6 regulates the production of selected bioactive media tors in allergic diseases. This is the first demonstration of a biologic fu nction of eIF-6 in mammalian cells.