Cooperation between PU.1 and CAAT/enhancer-binding protein beta is necessary to induce the expression of the MD-2 gene.
ABSTRACT Myeloid differentiation factor 2 (MD-2) binds Gram-negative bacterial lipopolysaccharide with high affinity and is essential for Toll-like receptor 4-dependent signal transduction. MD-2 has recently been recognized as a type II acute phase protein. Plasma concentrations of the soluble form of MD-2 increase markedly during the course of severe infections. Its production is regulated in hepatocytes and myeloid cells by interleukin-6 (IL-6) but not IL-1beta. In the present work we show that two transcription factors (TF), PU.1 and CAAT/enhancer-binding protein beta (C/EBPbeta), participate in the activation of the human MD-2 gene in hepatocytic cells after stimulation with IL-6. PU.1 TF and proximal PU.1 binding sites in the MD-2 promoter were shown to be critical for the basal activity of the promoter as well as for IL-6-induced soluble MD-2 production. Deletions of proximal portions of the MD-2 promoter containing PU.1 and/or NF-IL-6 consensus binding sites as well as site-directed mutagenesis of these binding sites abrogated IL-6-dependent MD-2 gene activation. We show that the cooperation between C/EBPbeta and PU.1 is critical for the transcriptional activation of the MD-2 gene by IL-6. PU.1 was essentially known as a TF involved in the differentiation of myeloid precursor cells and the expression of surface receptors of the innate immunity. Herein, we show that it also participates in the regulation of an acute phase protein, MD-2, in nonmyeloid cells cooperatively with C/EBPbeta, a classical IL-6-inducible TF.
Article: Safety and efficacy of contrast-enhanced MRI in the brain, head and neck: gadodiamide injection versus gadopentate dimeglumine.[show abstract] [hide abstract]
ABSTRACT: The objective of the present study was to evaluate the safety and efficacy of gadodiamide injection, a non ionic MRI contrast medium in comparison with the ionic agent gadopentate dimeglumine. Two groups of 50 patients with known or suspected lesions of the brain or head and neck were enrolled in a double -blind, randomised trial. In the gadopentate dimeglumine group three patients reported four adverse events, and in the gadodiamide injection group, four patients reported four side effects. All events were minor. Two radiologists analyzed pre and post-contrast MR images. The parameters evaluated were the number of lesions, delineation of the lesion, gain of diagnostic information, and final diagnosis. Both contrast media gave identical diagnostic information.Journal belge de radiologie 11/1997; 80(5):225-8.