Our research interest is focused on the molecular events ocurring in inflammatory cells for the defense against invading microbes. Reactive oxygen species are essential for killing most of bacteria, fungi, and parasites. We are therefore investigating mechanisms for the expression and activation of superoxide‐degenerating NADPH oxidase system.

GATA‐３ as the Eosinophil‐specific Repressor for the Expression of gp９１^phox, an Electrontransferring Component in Phagocyte NADPH Oxidase System
　　In a systematic search for cis‐elements regulating gp９１^phox exression in eosinophil lineage, we identified an inhibitory element containing a GATA consensus site at the proximal promoter and GATA‐３ as the specific protein binding to that site. Two‐base‐pair substitution at the consensus site abolished inhibition of the promoter activity in eosinophil‐committed HL６０‐C１５ cells, indicating that the GATA‐３ binding to the site is a repressor in the cells. Because eosinophil is the only cell expressing GATA‐３ among human phagocytes and B lymphocytes, GATA‐３ is an eosinophil lineage‐specific repressor of gp９１^phox gene.
　　

PU．１ but not HAF‐１ is a Common Activator for the Expression of gp９１^phox in Neutrophils, Monocytes and B Lymphocytes
　　For the expression of gp９１^phox in these cells, we previously suggested a common transcriptional activator which requires the position‐５３　based on an analysis of a novel patient with chronic granulomatous disease. HAF‐１ and PU．１ were indentified as candidates for this activator. We, therefore, examined ６０ fragments with onebase substitutions neighboring to‐５３， and found two sequences;one has a mutation at‐５６ and impairs the binding of HAF‐１，　and the other mutation at‐５０ and impairs the binding of PU．１ The‐５０ mutant promoter but not‐５６ mutant one exhibited decreased reporter activity, indicating PU．１， but not HAF‐１， to be an essential activator for the expression of the gene in those cells （Fig．１）．A discovery of a similar patient with a point mutation at‐５２ which abolished the binding of PU． １ confirmed our conclusion.
　　Our future aim is to apply these findings to in innovation of techniques to control tropical diseases and allergy.