PU.1 regulates glutathione peroxidase expression in neutrophils

Journal of Leukocyte Biology

Michael J. Klemsz¹  Stacy L. Throm¹ 

[1] Department of Microbiology and Immunology, Indiana University School of Medicine, and the Walther Cancer Institute, IndianapolisDepartment of Microbiology and Immunology, Indiana University School of Medicine, and the Walther Cancer Institute, IndianapolisDepartment of Microbiology and Immunology, Indiana University School of Medicine, and the Walther Cancer Institute, Indianapolis

关键词: transcription;    blood cell;    gene expression;   

DOI  :  10.1189/jlb.0203061

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Based on knockout models, the transcription factor PU.1 has been shown to be important for the maturation of neutrophils. As the list of genes PU.1 directly regulates in neutrophils is still quite limited, defining PU.1 target genes for this lineage will provide valuable insight into how this factor regulates neutrophil development and terminal function. Using the combined techniques of representational difference analysis and a cDNA library screen, we identified four genes that were differentially expressed in the PU.1-expressing 503PU myeloid cell line but not the PU.1 null parent cell line 503. Two of these genes, glutathione peroxidase (GPx) and serine leukoprotease inhibitor, are involved in protecting neutrophils from the products they make to destroy pathogens and were analyzed further to determine if PU.1 directly regulates their expression. These studies showed that PU.1 directly regulated the expression of only the GPx gene through binding sites in the promoter and a 3′ regulatory region. Thus, PU.1 not only regulates the expression of molecules involved in the production of reactive oxygen species but also a gene that protects the neutrophils from these same destructive enzymes.

【 授权许可】

Unknown