Eukaryotic translation initiation factor-6 enhances histamine and IL-2 production in mast cells.

Abstract

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.

• Authors: C K Oh, S G Filler, S H Cho
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 166 Issue 5 Pg. 3606-11 (Mar 01 2001) ISSN: 0022-1767 [Print] United States
• PMID: 11207322 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Interleukin-2
• Luminescent Proteins
• Peptide Initiation Factors
• RNA, Messenger
• Receptors, IgE
• eIF-6
• Green Fluorescent Proteins
• Interleukin-4
• Dexamethasone
• Histamine
• Cyclosporine
• Cycloheximide

Topics

• Animals
• Cell Line
• Cycloheximide (pharmacology)
• Cyclosporine (pharmacology)
• Dexamethasone (pharmacology)
• Gene Expression Regulation (drug effects, immunology)
• Genetic Vectors (biosynthesis)
• Green Fluorescent Proteins
• Histamine (biosynthesis)
• Histamine Release (genetics, immunology)
• Humans
• Immunosuppressive Agents (pharmacology)
• Interleukin-2 (biosynthesis, metabolism)
• Interleukin-4 (metabolism)
• Luminescent Proteins (genetics, metabolism)
• Mast Cells (drug effects, immunology, metabolism)
• Mice
• Peptide Initiation Factors (biosynthesis, genetics, physiology)
• RNA, Messenger (biosynthesis)
• Receptors, IgE (physiology)
• Transfection
• Up-Regulation (immunology)