Poor Expression (poor + expression)

Distribution by Scientific Domains


Selected Abstracts


Inefficient processing of mRNA for the membraneform of IgE is a genetic mechanism to limit recruitment of IgE-secreting cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2006
Alexander Karnowski
Abstract Immunoglobulin,E (IgE) is the key effector element in allergic diseases ranging from innocuous hay fever to life-threatening anaphylactic shock. Compared to other Ig classes, IgE serum levels are very low. In its membrane-bound form (mIgE), IgE behaves as a classical antigen receptor on B,lymphocytes. Expression of mIgE is essential for subsequent recruitment of IgE-secreting cells. We show that in activated, mIgE-bearing B,cells, mRNA for the membrane forms of both murine and human epsilon (,) heavy chains (HC) are poorly expressed compared to mRNA for the secreted forms. In contrast, in mIgG-bearing B,cells, mRNA for the membrane forms of murine gamma-1 (,1) and the corresponding human ,4 HC are expressed at a much higher level than mRNA for the respective secreted forms. We show that these findings correlate with the presence of deviant polyadenylation signal hexamers in the 3,,untranslated region (UTR) of both murine and human ,,genes, causing inefficient processing of primary transcripts and thus poor expression of the proteins and poor recruitment of IgE-producing cells in the immune response. Thus, we have identified a genetic steering mechanism in the regulation of IgE synthesis that represents a further means to restrain potentially dangerous, high serum IgE levels. [source]


Human NK cells display major phenotypic and functional changes over the life span

AGING CELL, Issue 4 2010
Magali Le Garff-Tavernier
Summary Aging is generally associated with an increased predisposition to infectious diseases and cancers, related in part to the development of immune senescence, a process that affects all cell compartments of the immune system. Although many studies have investigated the effects of age on natural killer (NK) cells, their conclusions remain controversial because the diverse health status of study subjects resulted in discordant findings. To clarify this situation, we conducted the first extensive phenotypic and functional analysis of NK cells from healthy subjects, comparing NK cells derived from newborn (cord blood), middle-aged (18,60 years), old (60,80 years), and very old (80,100 years) subjects. We found that NK cells in cord blood displayed specific features associated with immaturity, including poor expression of KIR and LIR-1/ILT-2 and high expression of both NKG2A and IFN-,. NK cells from older subjects, on the other hand, preserved their major phenotypic and functional characteristics, but with their mature features accentuated. These include a profound decline of the CD56bright subset, a specific increase in LIR-1/ILT-2, and a perfect recovering of NK-cell function following IL2-activation in very old subjects. We conclude that the preservation of NK cell features until very advanced age may contribute to longevity and successful aging. [source]


Gene expression analysis of macrophages derived from ankylosing spondylitis patients reveals interferon-, dysregulation

ARTHRITIS & RHEUMATISM, Issue 6 2008
Judith A. Smith
Objective To determine whether macrophages, a type of cell implicated in the pathogenesis of ankylosing spondylitis (AS), exhibit a characteristic gene expression pattern. Methods Macrophages were derived from the peripheral blood of 8 AS patients (median disease duration 13 years [range <1,43 years]) and 9 healthy control subjects over 7 days with the use of granulocyte,macrophage colony-stimulating factor. Cells were stimulated for 24 hours with interferon-, (IFN,; 100 units/ml), were left untreated for 24 hours, or were treated for 3 hours with lipopolysaccharide (LPS; 10 ng/ml). RNA was isolated and examined by microarray and real-time quantitative reverse transcription,polymerase chain reaction analysis. Results Microarray analysis revealed 198 probe sets detecting the differential expression of 141 unique genes in untreated macrophages from AS patients compared with healthy controls. Clustering and principal components analysis clearly distinguished AS patients and controls. Of the differentially expressed genes, 78 (55%) were IFN-regulated, and their relative expression indicated a "reverse" IFN signature in AS patient macrophages, where IFN,,up-regulated genes were underexpressed and down-regulated genes were overexpressed. Treatment of macrophages with exogenous IFN, normalized the expression of these genes between patients and controls. In addition, the messenger RNA encoded by the IFN, gene was ,2-fold lower in AS patient macrophages at baseline (P = 0.004) and was poorly responsive to LPS (P = 0.018), as compared with healthy controls. Conclusions Our findings reveal consistent differences in gene expression in macrophages from AS patients, with evidence of a striking "reverse" IFN signature. Together with poor expression and responsiveness of the IFN, gene, these results suggest that there may be a relative defect in IFN, gene regulation, with autocrine consequences and implications for disease pathogenesis. [source]


The in vivo synthesis of plant sesquiterpenes by Escherichia coli

BIOTECHNOLOGY & BIOENGINEERING, Issue 5 2001
Vincent J.J. Martin
Abstract Three plant genes encoding (+)-,-cadinene, 5- epi -aristolochene, and vetispiradiene cyclases were expressed in Escherichia coli to evaluate the potential of this bacterium to synthesize sesquiterpenes in vivo. Various growth temperatures, carbon sources, and host strains were examined to optimize terpene production. The highest levels of sesquiterpene production occurred when the enzymes were expressed in strain DH5, from the trc promoter (Ptrc) of the high-copy plasmidpTrc99A in M9 medium supplemented with 0.2% (v/v) glycerol at 30°C for 5- epi -aristolochene and vetispiradiene and 37°C for (+)-,-cadinene. The highest concentrations of sesquiterpenes observed were 10.3 ,g of (+)-,-cadinene, 0.24 ,g of 5- epi -aristolochene (measured as (+)-,-cadinene equivalents), and 6.4 ,g of vetispiradiene (measured as (+)-,-cadinene equivalents) per liter of culture. These sesquiterpene production levels are >500-fold lower than carotenoid production, both of which are synthesized from endogenous trans -farnesyl diphosphate (FDP) in E. coli. Based on these results, we conclude that the limiting factor for sesquiterpene synthesis in E. coli is the poor expression of the cyclase enzyme and not supply of the FDP precursor. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 497,503, 2001. [source]