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Summary Interferon Regulatory Factor 5 (IRF5) plays a major role in setting up an inflammatory macrophage phenotype, but the molecular basis of its transcriptional activity is not fully understood. In this study, we conduct a comprehensive genome-wide analysis of IRF5 recruitment in macrophages stimulated with bacterial lipopolysaccharide and discover that IRF5 binds to regulatory elements of highly transcribed genes. Analysis of protein:DNA microarrays demonstrates that IRF5 recognizes the canonical IRF-binding (interferon-stimulated response element [ISRE]) motif in vitro. However, IRF5 binding in vivo appears to rely on its interactions with other proteins. IRF5 binds to a noncanonical composite PU.1:ISRE motif, and its recruitment is aided by RelA. Global gene expression analysis in macrophages deficient in IRF5 and RelA highlights the direct role of the RelA:IRF5 cistrome in regulation of a subset of key inflammatory genes. We map the RelA:IRF5 interaction domain and suggest that interfering with it would offer selective targeting of macrophage inflammatory activities. [ABSTRACT FROM AUTHOR]

: BackgroundWe examined the effects of preoperative administration of enoxaparin (ENOX), a low-molecular-weight heparin, on bleeding indices and transfusion rates in patients undergoing coronary artery bypass grafting (CABG).: MethodsPatients undergoing isolated CABG between 1997 and 2002 who received preoperative ENOX or a continuous infusion of unfractionated heparin (UFH) were randomly divided into three groups: continuous UFH, ENOX last administered more than 12 hours before surgery (ENOX > 12), and ENOX administered less than 12 hours before surgery (ENOX < 12). Perioperative hemoglobin values, transfusion rates, and bleeding complications were compared.: ResultsA total of 69, 58, and 34 patients comprised the UFH, ENOX > 12, and ENOX < 12 groups, respectively. Preoperative demographics and hematologic data were similar among the groups. Compared with the UFH group, the ENOX < 12 group had significantly lower postoperative hemoglobin values (9.6 ± 1.3 g/dL versus 10.4 ± 1.2 g/dL, p < 0.05), higher transfusion rates (73.5% versus 50.7%, p < 0.05), and required more total packed red cells per patient (882 ± 809 mL versus 472 ± 626 mL, p < 0.05). A nonsignificant increase was noted in the risk of returning to the operating room for bleeding in patients who had received ENOX compared with patients receiving UFH (6.5% versus 2.9%).: ConclusionsThe preoperative use of ENOX less than 12 hours before CABG is associated with lower postoperative hemoglobin values and higher rates of transfusion than continuous UFH. [Copyright &y& Elsevier]

NF-κB is a key regulator of immune gene expression in metazoans. It is currently unclear what changes occurred in NF-κB during animal evolution and what features remained conserved. To address this question, we compared the biochemical and functional properties of NF-κB proteins derived from human and the starlet sea anemone (Nematostella vectensis) in 1) a high-throughput assay of in vitro preferences for DNA sequences, 2) ChIP analysis of in vivo recruitment to the promoters of target genes, 3) a LUMIER-assisted examination of interactions with cofactors, and 4) a transactivation assay. We observed a remarkable evolutionary conservation of the DNA binding preferences of the animal NF-κB orthologs. We also show that NF-κB dimerization properties, nuclear localization signals, and binding to cytosolic IκBs are conserved. Surprisingly, the Bcl3-type nuclear IκB proteins functionally pair up only with NF-κBderived from their own species. The basis of the differential NF-κB recognition by IκB subfamilies is discussed. [ABSTRACT FROM AUTHOR]