Microarray analysis of lipopolysaccharide-treated human neutrophils

2003 ◽  
Vol 284 (4) ◽  
pp. L663-L670 ◽  
Author(s):  
Kenneth C. Malcolm ◽  
Patrick G. Arndt ◽  
Elizabeth J. Manos ◽  
David A. Jones ◽  
G. Scott Worthen
Keyword(s):  
Gene Expression ◽  
Growth Regulation ◽  
Molecular Mechanisms ◽  
Neutrophil Function ◽  
Interferon Response ◽  
Human Neutrophils ◽  
Oxygen Intermediates ◽  
Microarray Gene Expression ◽  
Monocyte Chemoattractant Protein 1 ◽  
Cytokines And Chemokines

Neutrophils respond to infection by degranulation, release of reactive oxygen intermediates, and secretion of chemokines and cytokines; however, activation of neutrophil transcriptional machinery has been little appreciated. Recent findings suggest that gene expression may represent an additional neutrophil function after exposure to lipopolysaccharide (LPS). We performed microarray gene expression analysis of 4,608 mostly nonredundant genes on LPS-stimulated human neutrophils. Analysis of three donors indicated some variability but also a high degree of reproducibility in gene expression. Twenty-eight verifiable, distinct genes were induced by 4 h of LPS treatment, and 13 genes were repressed. Genes other than cytokines and chemokines are regulated; interestingly, genes involved in cell growth regulation and survival, transcriptional regulation, and interferon response are among those induced, whereas genes involved in cytoskeletal regulation are predominantly repressed. In addition, we identified monocyte chemoattractant protein-1 as a novel LPS-regulated chemokine in neutrophils. Included in these lists are five clones with no defined function. These data suggest molecular mechanisms by which neutrophils respond to infection and indicate that the transcriptional potential of neutrophils is greater than previously thought.

scholarly journals Network-Based Genetic Profiling Reveals Cellular Pathway Differences Between Follicular Thyroid Carcinoma and Follicular Thyroid Adenoma

2020 ◽  
Vol 17 (4) ◽  
pp. 1373 ◽  
Author(s):  
Md. Ali Hossain ◽  
Tania Akter Asa ◽  
Md. Mijanur Rahman ◽  
Shahadat Uddin ◽  
Ahmed A. Moustafa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Gene Expression Omnibus ◽  
Thyroid Adenoma ◽  
Hub Genes ◽  
Microarray Gene Expression ◽  
Genetic Profiling ◽  
Follicular Thyroid Adenoma ◽  
Pathway Analyses

Molecular mechanisms underlying the pathogenesis and progression of malignant thyroid cancers, such as follicular thyroid carcinomas (FTCs), and how these differ from benign thyroid lesions, are poorly understood. In this study, we employed network-based integrative analyses of FTC and benign follicular thyroid adenoma (FTA) lesion transcriptomes to identify key genes and pathways that differ between them. We first analysed a microarray gene expression dataset (Gene Expression Omnibus GSE82208, n = 52) obtained from FTC and FTA tissues to identify differentially expressed genes (DEGs). Pathway analyses of these DEGs were then performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) resources to identify potentially important pathways, and protein-protein interactions (PPIs) were examined to identify pathway hub genes. Our data analysis identified 598 DEGs, 133 genes with higher and 465 genes with lower expression in FTCs. We identified four significant pathways (one carbon pool by folate, p53 signalling, progesterone-mediated oocyte maturation signalling, and cell cycle pathways) connected to DEGs with high FTC expression; eight pathways were connected to DEGs with lower relative FTC expression. Ten GO groups were significantly connected with FTC-high expression DEGs and 80 with low-FTC expression DEGs. PPI analysis then identified 12 potential hub genes based on degree and betweenness centrality; namely, TOP2A, JUN, EGFR, CDK1, FOS, CDKN3, EZH2, TYMS, PBK, CDH1, UBE2C, and CCNB2. Moreover, transcription factors (TFs) were identified that may underlie gene expression differences observed between FTC and FTA, including FOXC1, GATA2, YY1, FOXL1, E2F1, NFIC, SRF, TFAP2A, HINFP, and CREB1. We also identified microRNA (miRNAs) that may also affect transcript levels of DEGs; these included hsa-mir-335-5p, -26b-5p, -124-3p, -16-5p, -192-5p, -1-3p, -17-5p, -92a-3p, -215-5p, and -20a-5p. Thus, our study identified DEGs, molecular pathways, TFs, and miRNAs that reflect molecular mechanisms that differ between FTC and benign FTA. Given the general similarities of these lesions and common tissue origin, some of these differences may reflect malignant progression potential, and include useful candidate biomarkers for FTC and identifying factors important for FTC pathogenesis.

Toll-Like Receptor 2 Signalling Regulates Oxidative Burst of Human Neutrophils, but Not Cytokine Response of Dendritic Cells after Contact with Aspergillus fumigatus.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3854-3854
Author(s):  
Juergen Loeffler ◽  
Markus Mezger ◽  
Iwona Wozniok ◽  
Oliver Kurzai ◽  
Hermann Einsele
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Aspergillus Fumigatus ◽  
Oxidative Burst ◽  
Fungal Infections ◽  
Human Neutrophils ◽  
Sirna Transfection ◽  
Oxygen Intermediates ◽  
Immature Dendritic Cells

Abstract Toll-like receptors (TLRs) play a crucial role for detecting conserved pathogen-associated molecular patterns comprising fungal structures. Activation of polymorphonuclear granulocytes (PMNs) as well as mobilization of antigen presenting cells is important for successful clearance of fungal infections. Here, the role of TLR2 and TLR4 for activation of PMNs and immature dendritic cells (iDCs) through Aspergillus fumigatus was analyzed. Generation of iDCs was achieved by cultivating monocytes in the presence of GM-CSF and IL-4. PMNs were obtained from fresh blood. In blocking studies, cells were preincubated with anti-TLR2 and / or anti-TLR4 antibody before stimulation with Aspergillus fumigatus germinating conidia. For RNA interference (RNAi) experiments, iDCs were transfected with short-interfering RNA (siRNA) via electroporation and gene expression was controlled by quantitative real-time PCR. Oxidative burst of PMNs was induced after contact with Aspergillus or TLR2 ligand zymosan. Release of oxygen intermediates could be significantly reduced if PMNs were preincubated with anti-TLR2 antibody. In contrast to monocytes, cytokine secretion (IL-12 and TNF-α) of iDCs was not altered if anti-TLR antibodies were used. To study the role of TLR2 and TLR4 more detailed, an RNAi system for iDCs was established to downregulate gene expression. Determination of siRNA transfection rate revealed an efficiency of about 85% and allowed significant downregulation of TLR2 and TLR4 (> 90%). In accordance to blocking studies, expression of IL-10, IL-12 and TNF-a was not reduced after TLR2 or TLR4 siRNA transfection and stimulation with Aspergillus. We conclude that TLR2 plays an important role in the induction of the oxidative burst of PMNs whereas cytokine release of iDCs seems to be independent of TLR2 / TLR4 signalling. The established siRNA system allows the detection of receptors responsible for activation of iDCs.

Conditional Deletion of the Hoxa Cluster in MLL-AF9 Is Incompatible with Leukemia Maintenance

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3630-3630
Author(s):  
Laura M Kettyle ◽  
Ivan Grishagin ◽  
Glenda J Dickson ◽  
Charles-Etienne Lebert-Ghali ◽  
Janetta Jacoba Bijl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colony Formation ◽  
Sanger Sequencing ◽  
Molecular Mechanisms ◽  
Cre Recombinase ◽  
Interferon Response ◽  
Interferon Α ◽  
Hoxa Cluster ◽  
Hematopoietic Stem ◽  
Pcr Products

Abstract Introduction Hox gene expression is high in hematopoietic stem/progenitor cells (HSPCs), decreases during normal differentiation but remains elevated in leukemia subtypes. Polycomb repressor complexes and histone modifiers, e.g. Mixed Lineage Leukemia (MLL), are key regulators of Hox expression. MLL rearrangements, frequent in acute leukemia, are associated high HOXA expression. However, necessity for the HoxA cluster in MLL-leukemia maintenance is not fully elucidated. Methodology Ectopic overexpression of MLL-AF9 (MA9) in HSPCs in conditional compound transgenic mouse backgrounds MxCre+/HoxAflox/flox (MAFF) or HoxAflox/flox (AFlox) models resulted in increased colony formation and growth in liquid culture. Transformed colonies, serially re-plated (n=5) in methylcellulose and transplanted into sub-lethally irradiated recipient mice, resulted in primary leukemia. Initially, MAFF-MA9 leukemias were used to examine in vivo deletion of the HoxA cluster using intraperitoneal injections of Poly(I:C) to initiate an interferon response. To further examine the necessity for the HoxA cluster in disease maintenance, AFlox-MA9 leukemias were treated ex vivo with Cre-recombinase (MSCV-Cre-GFP) or vector control (MSCV-GFP), sorted based on GFP expression and used for gDNA-PCR, gene expression (Illumina BeadArray) and transplantation into sub-lethally irradiated recipient mice (500 cGy). Results Generation of MLL-AF9 leukemias in the MAFF background (MAFF-MA9) resulted in deletion of one HoxA cluster allele (HoxA+/-), validated by genomic PCR and gDNA sequencing from expanded single colonies (Figure 1) presumably due to viral-induced activation of the Mx1 promoter. PolyI:C treatment of these mice resulted in a modest extension in survival (1-2 days) compared to controls. Luciferase labelling and transplantation of MAFF-MA9 leukemias into NSG mice, followed by PolyI:C treatment, showed a measurable decrease in disease burden compared to control, however this did not correlate with overall survival. Direct treatment of MAFF-MA9 cells with interferon-α (in vitro) resulted in further deletion of the HoxA cluster (HoxA-/hypo) and significant reduction in colony formation compared to controls. Although non-leukemic MAFF HSPCs retained colony forming ability after complete HoxA cluster deletion (HoxA-/-) no HoxA-/- colonies were recovered from the interferon-α treated MAFF-MA9 cultures. Cre-recombinase-induced deletion of the Hoxa cluster from AFlox-MA9 leukemia cells was confirmed by gDNA-PCR and sequencing (Figure 1). Transplantation of Cre-treated AFlox-MA9 cells resulted in significant increased survival (P<0.002) by up to 74 days in recipient mice, compared to controls (Figure 2). Further examination of the leukemias that developed from these Cre-treated AFlox-MA9 cells demonstrated retention of one allele of the HoxA cluster, as a result of escapees. To gain insight into the molecular mechanisms underlying the HoxA requirement for MLL-AF9 maintenance, matched Cre- or control treated AFlox-MA9 samples used for the transplantation were further examined for differential gene expression by Illumina BeadArray analysis. Preliminary analysis of the data has confirmed significant reduction in the expression of HoxA cluster genes (a2, a4, a5, a7, a9) and increased expression of several genes involved in adhesion, differentiation or immune response (e.g. Itgb3bp, Mpo, Cxcl2). Further analysis including submission of gene signatures to the LINCS database (https://www.broadinstitute.org/software/cprg/?q=node/40) will be done to identify candidate small molecules that mimic HoxA deletion in MLL-AF9. Conclusion Together these data support a fundamental role for the HoxA cluster in MLL-AF9 maintenance indicating dependency for this leukemia subtype which may be exploited for therapeutic benefit. Figure 1. Deletion of Hoxa cluster validated by Sanger sequencing. The chromatograph (A) and sequence obtained (B) from PCR products generated from primers used to detect Hoxa cluster deletion with retention of the 5' UTR and 3' UTR regions of the Hoxa13 and Hoxa1 genes respectively. Figure 1. Deletion of Hoxa cluster validated by Sanger sequencing. The chromatograph (A) and sequence obtained (B) from PCR products generated from primers used to detect Hoxa cluster deletion with retention of the 5' UTR and 3' UTR regions of the Hoxa13 and Hoxa1 genes respectively. Figure 2. Deletion of the Hoxa cluster results in significant increase in survival of Cre-GFPHi AFlox-MA9 mice compared to GFPhi control mice (n=10). Significance as calculated by Log-rank (Mantel-Cox) Test is denoted *** = p<0.001. Figure 2. Deletion of the Hoxa cluster results in significant increase in survival of Cre-GFPHi AFlox-MA9 mice compared to GFPhi control mice (n=10). Significance as calculated by Log-rank (Mantel-Cox) Test is denoted *** = p<0.001. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Glycosylphosphatidylinositol-Anchored Protease Sap9 Modulates the Interaction of Candida albicans with Human Neutrophils

2009 ◽  
Vol 77 (12) ◽  
pp. 5216-5224 ◽  
Author(s):  
Anke Hornbach ◽  
Antje Heyken ◽  
Lydia Schild ◽  
Bernhard Hube ◽  
Jürgen Löffler ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Molecular Mechanisms ◽  
Immune Defense ◽  
Polymorphonuclear Neutrophils ◽  
Human Neutrophils ◽  
Oxygen Intermediates ◽  
Host Interaction ◽  
Adhesion Tissue ◽  
Human Pmns ◽  
Induced Apoptosis

ABSTRACTHuman polymorphonuclear neutrophils (PMNs) play a major role in the immune defense against invasiveCandida albicansinfection. This fungal pathogen produces a set of aspartic proteases that directly contributes to virulence properties such as adhesion, tissue invasion, and immune evasion. We show here that, in contrast to other secreted proteases, the cell surface-associated isoform Sap9 has a major impact on the recognition ofC. albicansby PMNs.SAP9is required for the induction of PMN chemotaxis towardC. albicansfilaments, an essential prerequisite of effective PMN activation. Furthermore, deletion ofSAP9leads to a mitigated release of reactive oxygen intermediates (ROI) in human PMNs and decreasesC. albicans-induced apoptosis triggered by ROI formation. In confrontation assays, killing of aSAP9deletion mutant is reduced in comparison to wild-typeC. albicans. These data clearly implicate Sap9 protease activity in the initiation of protective innate immunity and suggest novel molecular mechanisms inC. albicans-host interaction leading to neutrophil activation.

scholarly journals Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 191 ◽  
Author(s):  
Md. Rezanur Rahman ◽  
Tania Islam ◽  
Md. Shahjaman ◽  
Toyfiquz Zaman ◽  
Hossain Md. Faruquee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Interaction Analysis ◽  
Mapk Signaling ◽  
Protein Protein Interactions ◽  
Microarray Gene Expression ◽  
Pathway Analyses

Background and objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disease that results in severe dementia. Having ischemic strokes (IS) is one of the risk factors of the AD, but the molecular mechanisms that underlie IS and AD are not well understood. We thus aimed to identify common molecular biomarkers and pathways in IS and AD that can help predict the progression of these diseases and provide clues to important pathological mechanisms. Materials and Methods: We have analyzed the microarray gene expression datasets of IS and AD. To obtain robust results, combinatorial statistical methods were used to analyze the datasets and 26 transcripts (22 unique genes) were identified that were abnormally expressed in both IS and AD. Results: Gene Ontology (GO) and KEGG pathway analyses indicated that these 26 common dysregulated genes identified several altered molecular pathways: Alcoholism, MAPK signaling, glycine metabolism, serine metabolism, and threonine metabolism. Further protein–protein interactions (PPI) analysis revealed pathway hub proteins PDE9A, GNAO1, DUSP16, NTRK2, PGAM2, MAG, and TXLNA. Transcriptional and post-transcriptional components were then identified, and significant transcription factors (SPIB, SMAD3, and SOX2) found. Conclusions: Protein–drug interaction analysis revealed PDE9A has interaction with drugs caffeine, γ-glutamyl glycine, and 3-isobutyl-1-methyl-7H-xanthine. Thus, we identified novel putative links between pathological processes in IS and AD at transcripts levels, and identified possible mechanistic and gene expression links between IS and AD.

Long-Lasting Dysregulation of the Hematopoietic Stem Cell Compartment in Obesity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 245-245
Author(s):  
Jung-Mi Lee ◽  
Bryan Goddard ◽  
Ashwini S. Hinge ◽  
Bruce J. Aronow ◽  
Nathan Salomonis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Molecular Mechanisms ◽  
Interferon Response ◽  
Compensatory Mechanisms ◽  
Hematopoietic Stem ◽  
Genome Wide ◽  
A Genome ◽  
The Impact

Abstract Obesity is a complex pathological state defined by the excessive accumulation of adipose tissue and an array of hormonal, immunological and metabolic dysregulations. As such, obesity is a systemic stress that directly affects numerous organs and tissues. Notably, obesity and its sequelae modulate the immune system and the hematopoietic activity in the bone marrow (BM). Not surprisingly, obesity is also a well-established risk factor for leukemia associated with increased incidence and poor prognosis. However, despite their clinical relevance, mechanisms by which obesity affects the hematopoietic system remain elusive. Particularly, the impact of obesity on the hematopoietic stem cell (HSC) compartment has not been described. Using genetic and dietary mouse models of obesity, we conducted a "HSC-centered study" to determine how obesity affects HSCs and how these cells develop specific compensatory mechanisms to respond to this environment. Although HSCs in an obese environment displayed limited phenotypic and functional perturbations at steady state, they showed an aberrant response to hematopoietic stresses. In serial competitive transplantation assays, obesity-primed HSCs (defined as Lin- Sca-1+ c-Kit+ CD48- CD150+) showed a higher level of engraftment than controls in primary recipient mice (control, 20.8% +/-6.2 vs obese, 45.5% +/-14.6, p=0.022) but a dramatically reduced level of engraftment in secondary recipient mice (control: 25.8% +/-14.0 vs obese: 5.4% +/-3.9, p=0.033). Interestingly, BM analysis of secondary recipients showed reduced chimerism in all hematopoietic compartments but not in the HSC compartment. Altogether these results uncovered a biphasic behavior of the obesity-primed HSCs, characterized by an excessive differentiation response followed by a functional decline in which HSCs self-renew but fail to produce downstream progenitors. To unveil the molecular mechanisms involved in this aberrant activity, we performed a genome-wide gene expression analysis on HSCs isolated from normal and obese mice. Although the phenotype observed upon serial transplantation partially mimics HSC aging, obesity-primed HSCs did not share the molecular signature of old HSCs. Furthermore, down-regulation of interferon response-related genes (e.g Irak4, Irf7, Ifi27) and stress response-related genes (e.g. Stip1, Cgrrf1) showed that, unlike what has been described for committed progenitors, HSCs do not elicit a dramatic response to the inflammatory environment associated with obesity. In contrast obesity leads to the activation of specific molecular programs in HSCs. Firstly, obesity-primed HSCs showed up-regulation of multiples genes involved in the phosphatidylinositol signaling pathway (e.g. Pi4ka, Pi4k2b, Pi3kap1, Pi3kip1). Phosphoflow cytometry analysis indicated that this gene expression pattern was associated with the constitutive activation of the protein kinase AKT. While AKT activation is linked to functional HSC exhaustion, obesity-primed HSCs appeared refractory to this signal, suggesting the existence of compensatory mechanisms that protect the integrity of the HSCs in an obese environment. In parallel, we found that the aberrant activity of the obesity-primed HSCs was correlated with an elevated expression of Gfi1, a transcription factor critical for HSC quiescence and differentiation. Interestingly, the 2-fold increase in Gfi1 expression (p<10-5) observed in obesity-primed HSCs was maintained after serial transplantations in normal recipient mice indicating that the obese environment was able to promote the selection of a stable molecular program in the HSC compartment. Consistent with this idea, single-cell genome-wide analyses suggested a significant clonal shift within the obesity-primed HSC compartment. Finally, consistent with epidemiological data, we found that disruption of HSC homeostasis by obesity promotes the development of spontaneous hematopoietic pathologies resembling to myeloproliferative diseases. Altogether, our results establish the long lasting impact of obesity on the HSC compartment and uncover potential molecular mechanisms linking obesity to hematological diseases. Notably our results support the intriguing possibility that obesity, by directly acting on the HSC compartment, contributes to the development of a clonal hematopoiesis and favors the emergence of aberrant HSC clones. Disclosures No relevant conflicts of interest to declare.

Contribution of microarrays of gene expression (MAGE) to the definition of PET/CT as a qualified biomarker of early response in metastatic patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11573-11573
Author(s):  
Manuel Sureda ◽  
Aurora Crespo-Jara ◽  
Ramon Gonzalez Manzano ◽  
Maria del Carmen Redal ◽  
Francisco Javier Garcia-Cases ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fdg Pet ◽  
Ribosome Biogenesis ◽  
Molecular Mechanisms ◽  
Gene Expression Signature ◽  
Early Response ◽  
Biological Processes ◽  
Microarray Gene Expression ◽  
Fdg Uptake ◽  
Pet Ct

11573 Background: Proliferating cancer cells consume elevated quantity of glucose, converted into lactate regardless the presence of oxygen (Warburg effect). This effect has been useful for imaging metabolically active tumors with FDG-PET, although its use in early response is controversial. Molecular mechanisms of FDG uptake are not fully understood. We have used MAGE to determine the most relevant genes involved in FDG uptake. Methods: Fresh-frozen tumor biopsies and quantitative basal FDG-PET/CT were obtained from metastatic lesions in cancer patients. Total tumor RNA was hybridized to a whole human genome oligonucleotide microarray. Gene expression signature-based prediction, using the most relevant genes involved in FDG uptake measured by SUV, was finally determined by Partial Least Squares (PLS). The interpretation of biological phenomena (IBP) derived from the selected genes was made by means of different public statistical bioinformatics resources. Results: 71 patients with different histological diagnosis were included in the training cohort and 13 in the validation one. 909 probes correlated significantly with SUV: 333 positively and 576 negatively. A predictive signature based on these 909 probes was built using PLS-3, with an RMSE in the validation set of 0.645 (within the 95% CI of RMSE determined in the training set). In IBP, other biological processes were more relevant than glycolysis in FDG uptake: RNA processing, ribosome biogenesis, protein processing, cell adhesion, cytoskeleton organization, angiogenesis and autophagy. Conclusions: This PLS-3-built signature is the first reported one that can accurately predict SUV. FDG uptake is a complex phenomenon that involves multiple biological processes, confirming the value of PET/CT in early response.

scholarly journals Differential Ability of Pandemic and Seasonal H1N1 Influenza A Viruses To Alter the Function of Human Neutrophils

mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Natalia Malachowa ◽  
Brett Freedman ◽  
Daniel E. Sturdevant ◽  
Scott D. Kobayashi ◽  
Vinod Nair ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bactericidal Activity ◽  
Influenza A ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Fungal Infections ◽  
Neutrophil Function ◽  
Human Neutrophils ◽  
Influenza A Viruses ◽  
Content Type

ABSTRACTNeutrophils are essential cells of host innate immunity. Although the role of neutrophils in defense against bacterial and fungal infections is well characterized, there is a relative paucity of information about their role against viral infections. Influenza A virus (IAV) infection can be associated with secondary bacterial coinfection, and it has long been posited that the ability of IAV to alter normal neutrophil function predisposes individuals to secondary bacterial infections. To better understand this phenomenon, we evaluated the interaction of pandemic or seasonal H1N1 IAV with human neutrophils isolated from healthy persons. These viruses were ingested by human neutrophils and elicited changes in neutrophil gene expression that are consistent with an interferon-mediated immune response. The viability of neutrophils following coculture with either pandemic or seasonal H1N1 IAV was similar for up to 18 h of culture. Notably, neutrophil exposure to seasonal (but not pandemic) IAV primed these leukocytes for enhanced functions, including production of reactive oxygen species and bactericidal activity. Taken together, our results are at variance with the universal idea that IAV impairs neutrophil function directly to predispose individuals to secondary bacterial infections. Rather, we suggest that some strains of IAV prime neutrophils for enhanced bacterial clearance.IMPORTANCEA long-standing notion is that IAV inhibits normal neutrophil function and thereby predisposes individuals to secondary bacterial infections. Here we report that seasonal H1N1 IAV primes human neutrophils for enhanced killing ofStaphylococcus aureus. Moreover, we provide a comprehensive view of the changes in neutrophil gene expression during interaction with seasonal or pandemic IAV and report how these changes relate to functions such as bactericidal activity. This study expands our knowledge of IAV interactions with human neutrophils.

scholarly journals Gene expression variation between African Americans and whites is associated with coronary artery calcification: the multiethnic study of atherosclerosis

2011 ◽  
Vol 43 (13) ◽  
pp. 836-843 ◽  
Author(s):  
Chiang-Ching Huang ◽  
Donald M. Lloyd-Jones ◽  
Xiuqing Guo ◽  
Nalini M. Rajamannan ◽  
Simon Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coronary Artery ◽  
African Americans ◽  
Inflammatory Response ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Intima Media Thickness ◽  
Epidemiological Data ◽  
Differentially Expressed ◽  
Microarray Gene Expression

Coronary artery calcium (CAC) is a strong indicator of total atherosclerosis burden. Epidemiological data have shown substantial differences in CAC prevalence and severity between African Americans and whites. However, little is known about the molecular mechanisms underlying initiation and progression of CAC. Microarray gene expression profiling of peripheral blood leucocytes was performed from 119 healthy women aged 50 yr or above in the Multi-Ethnic Study of Atherosclerosis cohort; 48 women had CAC score >100 and carotid intima-media thickness (IMT) >1 mm, while 71 had CAC <10 and IMT <0.65 mm. When 17 African Americans were compared with 41 whites in the low-CAC group, 409 differentially expressed genes (false discovery rate <5%)were identified. In addition, 316 differentially expressed genes were identified between the high- and low-CAC groups. A substantial overlap between these two gene lists was observed (148 genes, P < 10−6). Furthermore, genes expressed lower in African Americans also tend to express lower in individuals with low CAC (correlation 0.69, P = 0.002). Ontology analysis of the 409 race-associated genes revealed significant enrichment in mobilization of calcium and immune/inflammatory response ( P < 10−9). Of note, 25 of 30 calcium mobilization genes were involved in immune/inflammatory response ( P < 10−10). Our data suggest a connection between immune response and vascular calcification and the result provides a potential mechanistic explanation for the lower prevalence and severity of CAC in African Americans compared with whites.

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