During this reporting period, we examined the roles of GATA-1 and GATA-2 in activating transcription of the secretory ribonuclease, the eosinophil-derived neurotoxin (EDN/RNase 2). Augmented expression of both GATA-1 and GATA-2 was detected in eosinophils and deletion or mutation of one or both of the two consensus GATA-binding sites in the extended 5'promoter of the EDN/RNase2 gene resulted in profound reduction in reporter gene activity. Antibody-augmented electrophoretic mobility shift and chromatin immunoprecipitation analyses indicate that GATA-1 and GATA-2 proteins bind to both functional GATA consensus sequences in the EDN promoter. Interestingly, RNA silencing of GATA-1 alone had no impact on EDN/RNase2 expression;silencing of GATA-2 resulted in diminished expression of EDN, and also diminished expression of GATA-1 in both butyric acid-induced HL-60 clone 15 cells and in differentiating human eosinophils derived from CD34(+) hematopoietic progenitors. Likewise, overexpression of GATA-2 in resulted in augmented transcription of both EDN/RNase2 and GATA-1. Taken together, our data suggest that GATA-2 functions directly via interactions with the EDN promoter and also indirectly, via its ability to regulate the expression of GATA-1 in differentiating eosinophils (Qiu et al. J Biol Chem. 2009). Another publication focuses on the diversity of mammalian RNase A ribonucleases, and completes some outstanding work from Dr. Wei Zhao's visiting professorship with our group. This manuscript, which identifies a novel cluster of rodent RNase 1 genes, serves also to complete and to correct several erroneous entries in GenBank database (Siegel et al. Mamm Genome, 2009, in press) I continue to serve on the Editorial Board of Journal of Biological Chemistry (since 2008), a largely due to my expertise in Ribonuclease Biology and Biochemistry.

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Rosenberg, Helene F; Druey, Kirk M (2018) Modeling asthma: Pitfalls, promises, and the road ahead. J Leukoc Biol 104:41-48
Ma, M; Redes, J L; Percopo, C M et al. (2018) Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection. Clin Exp Allergy 48:691-702
Foster, Paul S; Maltby, Steven; Rosenberg, Helene F et al. (2017) Modeling TH 2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma. Immunol Rev 278:20-40
Percopo, Caroline M; Brenner, Todd A; Ma, Michelle et al. (2017) SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice. J Leukoc Biol 101:321-328
Kraemer, Laura S; Brenner, Todd A; Krumholz, Julia O et al. (2017) A flow-cytometric method to evaluate eosinophil-mediated uptake of probiotic Lactobacillus reuteri. J Microbiol Methods 137:19-24
Rosenberg, Helene F; Druey, Kirk M (2016) Eosinophils, galectins, and a reason to breathe. Proc Natl Acad Sci U S A 113:9139-41
Rosenberg, Helene F (2015) Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host Defense. Int J Mol Sci 16:15442-55
Yamada, Kelsey J; Barker, Tolga; Dyer, Kimberly D et al. (2015) Eosinophil-associated ribonuclease 11 is a macrophage chemoattractant. J Biol Chem 290:8863-75
Percopo, Caroline M; Dyer, Kimberly D; Ochkur, Sergei I et al. (2014) Activated mouse eosinophils protect against lethal respiratory virus infection. Blood 123:743-52
Yang, Ming; Eyers, Fiona; Xiang, Yang et al. (2014) Expression profiling of differentiating eosinophils in bone marrow cultures predicts functional links between microRNAs and their target mRNAs. PLoS One 9:e97537

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