scholarly journals Growth, photosynthesis, and gene expression in Chlamydomonas over a range of CO2 concentrations and CO2/O2 ratios: CO2 regulates multiple acclimation states

2005 ◽  
Vol 83 (7) ◽  
pp. 796-809 ◽  
Author(s):  
Peter Vance ◽  
Martin H Spalding
Keyword(s):  
Gene Expression ◽  
Doubling Time ◽  
Wild Type ◽  
Airlift Bioreactors ◽  
Cell Doubling Time ◽  
Glycolate Dehydrogenase ◽  
Type C ◽  
Induced Genes ◽  
Inducible Genes

Growth, photosynthesis, and induction of two low CO2-inducible genes of Chlamydomonas reinhardtii Dangeard strain CC125 were quantified in a range of physiologically relevant CO2 and O2 concentrations (5%–0.005% CO2 and 20% or 2% O2) using airlift bioreactors to facilitate the simultaneous measurement of both growth and in situ photosynthetic rates. Within these CO2 concentration ranges, O2 concentrations (20% vs. 2%) had no discernable effect on growth, photosynthetic rate, or induction of the periplasmic carbonic anhydrase (Cah1) and glycolate dehydrogenase (Gdh) genes in wild-type C. reinhardtii. These results failed to support the hypothesis that the CO2/O2 ratio plays any role in signaling for the up-regulation of limiting CO2-induced genes and (or) of the CO2-concentrating mechanism (CCM). The mRNA abundance of the Cah1 and Gdh genes appeared to be regulated in concert, suggesting co-regulation by the same signaling pathway, which, because of a lack of an O2 effect, seems unlikely to involve photorespiration or a photorespiratory metabolite. Instead, it appeared that the CO2 concentration alone was responsible for regulation of limiting CO2 acclimation responses. Based on growth, photosynthesis, and gene expression characteristics, three distinct CO2-regulated physiological states were recognized within the studied parameters, a high CO2 (5%–0.5%) state, a low CO2 (0.4%–0.03%) state, and a very low CO2 (0.01%–0.005%) state. Induction of Cah1 expression and Gdh up-regulation occurred at a CO2 concentration between 0.5% and 0.4% CO2, delineating the high from the low CO2 states. Photosynthetic characteristics also were distinct in the three CO2-regulated physiological states, e.g., the estimated K0.5(CO2) of the high CO2, low CO2, and very low CO2 states were 72, 10, and 0.9 µmol·L–1 CO2, respectively. In addition to a greater photosynthetic CO2 affinity, the very low CO2 state could be distinguished from the low CO2 state by an increased cell-doubling time and a smaller cell size.Key words: algae, Chlamydomonas, CO2, gene expression, induction, photorespiration, photosynthesis.

scholarly journals CEBPA Gene Mutations Interfere with Expressions of NKG2D Ligands Ulbps in AML Cells and Modulate Their Susceptibility to NK-Mediated Lysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1257-1257
Author(s):  
Meng Liu ◽  
Limengmeng Wang ◽  
Huafang Wang ◽  
Shan Fu ◽  
He Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Germ Line ◽  
Gene Expression Microarray ◽  
Wild Type ◽  
Expression Microarray ◽  
Over Expression ◽  
Microarray Profiling ◽  
Type C ◽  
Profiling Analysis

Introduction: CEBPA gene encodes CCAAT/enhancer-binding protein-alpha (C/EBPα), a crucial granulocytic differentiation factor and tumor suppressor in hematologic and many non-hematologic malignancies. We previously reported a donor-derived relapse of AML patient after allogeneic hematopoietic stem cell transplantation with multiple mutations in CEBPA gene: a N-terminal frameshift mutation (247dupC causing overproduction of truncated 30-KDa isoform, lacking the TAD1 domain, p30), a N-terminal germ-line mutation (584_589dup disrupting the TAD2 domain of protein, NM2), and a C-terminal mutation (914_916dup disrupting the bZIP domain, CM) (Blood 2011; 117: 5257-5260). Although studies from multiple laboratories have contributed immensely to our understanding that how different CEBPA mutations disturb C/EBPα functions including granulopoiesis and leukemic transformation in AML, whether C/EBPα might regulate immunosurveillance remains unknown. Methods: AML cell line cells infected with lentivirus to over-express of wild type C/EBPα as well as 3 types of C/EBPα mutants were co-cultured with NK92MI cells and detected cytotoxic lysis through FCM. NK92MI cells were stained with CD107a to detect degranulation.We performed gene expression microarray profiling analysis in AML cell line cells with over-expression of wild type C/EBPα and mutants . Flag tagged wide type C/EBPα was over-expressed in 293T cells and ChIP with anti-Flag antibody followed by sequencing assay was performed to explore candidate gene binding sites of C/EBPα. Finally, independent ChIP-qPCR of candidate sequences were performed to further verify the transcription factor binding sites of C/EBPα. Results: ULBPs expressed on the surface of tumor or infected cells are important ligands of NK cell receptor NKG2D. Our gene expression microarray profiling analysis showed that wild type C/EBPα could up-regulate the expression of ULBP2/5/6 in AML cell line cells. Consistent with the results of gene expression microarray profiling analysis, over-expression of wild type C/EBPα and a N-terminal germ-line mutant (NM2) can up-regulate ULBP2/5/6 expression in NB4 cells, whose endogenous expression of ULBPs was low. Meanwhile, the sensitivities of NB4 cells to the cytotoxicity of NK92MI cells were also increased by over-expression of wide type C/EBPα and NM2 mutant. In contrast, leukemia-associated somatic mutations, C/EBPα p30 and C-terminal mutant (CM), were disabled to up-regulate ULBPs expression. In dual-luciferase reporter assay, the ratio of level of firefly luciferase and renilla luciferase significantly increased when co-transduced report plasmid with wide type C/EBPα expressing plasmid compared with vector control, indicating that C/EBPα could up-regulate the transcription of ULBP2 as a transcription factor. Through ChIP-seq assay we identified 12 peaks nearby ULBP genes in chromosome 6. We further performed ChIP-qPCR to target the sequences acting as enhancers of ULBP genes, which located +7kb upstream of transcription start site of ULBP2 gene, +11kb upstream of ULBP5 gene, -9kb downstream of ULBP6 gene and -40kb downstream of ULBP1 gene. Wide type C/EBPα showed higher binding affinity to the ULBP2/5 enhancers with more than 50 folds' enrichment and to the ULBP6/1 enhancers 9 folds' enrichment compared with IgG control. The N-terminal germ-line mutant (NM2) conserved part of the binding affinity, but the enrich fold was lower than wide type. As expected, leukemia-associated C-terminal mutant (CM) totally lost its binding ability to both sequences due to the damage of DNA binding domain. Althoughleukemia-associated truncated 30-KDa isoform partly conserved its binding ability to these DNA sequences, the mutant lost the function of regulating ULBPs expression. Conclusions: C/EBPα played an important role in innate immunosurveillance of AML. C/EBPα could bind to the promoter and potential enhancers of ULBP genes as a transcription factor, up-regulate expression of ULBPs and eventually induce AML cells to be recognized and killed by NK cells. Mutations in TAD2 domain did not affect this regulation function, while mutations in TAD1 and bZIP domain lost the specific ability. Leukemia cells with N-terminal frameshift mutations (p30), or C-terminal mutations could escape from surveillance of NK cells and may play pivotal roles in leukemia relapse. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Novel Mouse HSF3 Has the Potential to Activate Nonclassical Heat-Shock Genes during Heat Shock

2010 ◽  
Vol 21 (1) ◽  
pp. 106-116 ◽  
Author(s):  
Mitsuaki Fujimoto ◽  
Naoki Hayashida ◽  
Takuma Katoh ◽  
Kouji Oshima ◽  
Toyohide Shinkawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heat Shock ◽  
Cell Survival ◽  
Null Mouse ◽  
Wild Type ◽  
Heat Shock Genes ◽  
Embryonic Fibroblasts ◽  
Large Numbers ◽  
Inducible Genes ◽  
Transcription Factor 1

The heat-shock response is characterized by the expression of a set of classical heat-shock genes, and is regulated by heat-shock transcription factor 1 (HSF1) in mammals. However, comprehensive analyses of gene expression have revealed very large numbers of inducible genes in cells exposed to heat shock. It is believed that HSF1 is required for the heat-inducible expression of these genes although HSF2 and HSF4 modulate some of the gene expression. Here, we identified a novel mouse HSF3 (mHSF3) translocated into the nucleus during heat shock. However, mHSF3 did not activate classical heat-shock genes such as Hsp70. Remarkably, overexpression of mHSF3 restored the expression of nonclassical heat-shock genes such as PDZK3 and PROM2 in HSF1-null mouse embryonic fibroblasts (MEFs). Although down-regulation of mHSF3 expression had no effect on gene expression or cell survival in wild-type MEF cells, it abolished the moderate expression of PDZK3 mRNA and reduced cell survival in HSF1-null MEF cells during heat shock. We propose that mHSF3 represents a unique HSF that has the potential to activate only nonclassical heat-shock genes to protect cells from detrimental stresses.

scholarly journals The effect of neurogenin3 deficiency on pancreatic gene expression in embryonic mice

2006 ◽  
Vol 37 (2) ◽  
pp. 301-316 ◽  
Author(s):  
Andreas Petri ◽  
Jonas Ahnfelt-Rønne ◽  
Klaus Stensgaard Frederiksen ◽  
David George Edwards ◽  
Dennis Madsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Molecular Mechanisms ◽  
Homeobox Gene ◽  
Specific Gene ◽  
Wild Type ◽  
Specific Gene Expression ◽  
And Function ◽  
Deficient Mice

To understand the molecular mechanisms regulating pancreatic endocrine development and function, pancreatic gene expression was compared between Ngn3-deficient mice and littermate controls on embryonic days 13 and 15. Microarray analysis identified 504 genes with significant differences in expression. Fifty-two of these showed at least twofold reduction in Ngn3 knockouts compared to controls. Many of them were previously described to be involved in endocrine development and function. Among the genes not previously characterized were Rhomboid veinlet-like 4, genes involved in tetrahydrobiopterin biosynthesis and the Iroquois-type homeobox gene Irx1, the latter was selected for further investigation. In situ hybridisation demonstrated that two Iroquois genes, Irx1 and Irx2, were expressed in pancreatic endoderm of wild-type, but not Ngn3 mutant embryos. Furthermore, ectopic Ngn3 induced prominent Irx2 expression in chicken endoderm. Co-labelling established that Irx1 and Irx2 mRNA is located to glucagon-, but not insulin- or somatostatin-producing cells in mice and chicken. These data suggest that Irx1 and Irx2 serve an evolutionary conserved role in the regulation of α-cell-specific gene expression.

scholarly journals A Nonessential HP1-Like Protein Affects Starvation-Induced Assembly of Condensed Chromatin and Gene Expression in Macronuclei of Tetrahymena thermophila

1999 ◽  
Vol 19 (5) ◽  
pp. 3624-3634 ◽  
Author(s):  
Hui Huang ◽  
James F. Smothers ◽  
Emily A. Wiley ◽  
C. David Allis
Keyword(s):  
Gene Expression ◽  
Tetrahymena Thermophila ◽  
Morphological Changes ◽  
Condensed Chromatin ◽  
Induced Response ◽  
Wild Type ◽  
Eukaryotic Genes ◽  
Associated Proteins ◽  
Induced Genes ◽  
Dense Chromatin

ABSTRACT Heterochromatin represents a specialized chromatin environment vital to both the repression and expression of certain eukaryotic genes. One of the best-studied heterochromatin-associated proteins isDrosophila HP1. In this report, we have disrupted all somatic copies of the Tetrahymena HHP1 gene, which encodes an HP1-like protein, Hhp1p, in macronuclei (H. Huang, E. A. Wiley, R. C. Lending, and C. D. Allis, Proc. Natl. Acad. Sci. USA 95:13624–13629, 1998). Unlike the Drosophila HP1 gene,HHP1 is not essential in Tetrahymena spp., and during vegetative growth no clear phenotype is observed in cells lacking Hhp1p (ΔHHP1). However, during a shift to nongrowth conditions, the survival rate of ΔHHP1 cells is reduced compared to that of wild-type cells. Upon starvation, Hhp1p becomes hyperphosphorylated concomitant with a reduction in macronuclear volume and an increase in the size of electron-dense chromatin bodies; neither of these morphological changes occurs in the absence of Hhp1p. Activation of two starvation-induced genes (ngoA and CyP) is significantly reduced in ΔHHP1 cells while, in contrast, the expression of several growth-related or constitutively expressed genes is comparable to that in wild-type cells. These results suggest that Hhp1p functions in the establishment and/or maintenance of a specialized condensed chromatin environment that facilitates the expression of certain genes linked to a starvation-induced response.

scholarly journals Mutations in SIX1 associated with Branchio-oto-renal Syndrome (BOR) differentially affect otic expression of putative target genes

2021 ◽  
Author(s):  
Tanya Mehdizadeh ◽  
Himani Datta Majumdar ◽  
Sahra Ahsan ◽  
Andre Luiz Pasqua Tavares ◽  
Sally A Moody
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Otic Vesicle ◽  
Wild Type ◽  
Single Nucleotide ◽  
Putative Target ◽  
Individual Effects ◽  
Factor Interactions ◽  
Ability To Drive

Single nucleotide mutations in SIX1 are causative in some individuals diagnosed with branchiootic/branchio-oto-renal (BOR) syndrome. To test whether these mutations have differential effects on otic gene expression, we engineered four BOR mutations in Xenopus six1 and targeted mutant protein expression to the neural crest and cranial placode precursor cells in wild-type embryos. Changes in the otic expression of putative Six1 targets and/or co-factors were monitored by qRT-PCR and in situ hybridization. We found that each mutant had a different combination of effects. The V17E mutant reduced eya2, tspan13, zbtb16 and pa2g4 otic vesicle expression at a frequency indistinguishable from wildtype Six1, but reduced prdm1 more and spry1 less compared to wild-type Six1. For most of these genes, the R110W, W122R and Y129C mutants were significantly less repressive compared to wild-type Six1. Their individual effects varied according to the level at which they were expressed. The R110W, W122R and Y129C mutants also often expanded prdm1 otic expression. Since previous studies showed that all four mutants are transcriptionally deficient and differ in their ability to interact with co-factors such as Eya1, we propose that altered co-factor interactions at the mutated sites differentially interfere with their ability to drive otic gene expression.

scholarly journals Effect of peripheral administration of cholecystokinin on food intake in apolipoprotein AIV knockout mice

2012 ◽  
Vol 302 (11) ◽  
pp. G1336-G1342 ◽  
Author(s):  
Go Yoshimichi ◽  
Chunmin C. Lo ◽  
Kellie L. K. Tamashiro ◽  
Liyun Ma ◽  
Dana M. Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Food Intake ◽  
Food System ◽  
Nucleus Tractus Solitarius ◽  
Wild Type ◽  
Post Hoc Analysis ◽  
Nodose Ganglia ◽  
Post Hoc ◽  
The Brain

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are satiation factors secreted by the small intestine in response to lipid meals. Apo AIV and CCK-8 has an additive effect to suppress food intake relative to apo AIV or CCK-8 alone. In this study, we determined whether CCK-8 (1, 3, or 5 μg/kg ip) reduces food intake in fasted apo AIV knockout (KO) mice as effectively as in fasted wild-type (WT) mice. Food intake was monitored by the DietMax food system. Apo AIV KO mice had significantly reduced 30-min food intake following all doses of CCK-8, whereas WT mice had reduced food intake only at doses of 3 μg/kg and above. Post hoc analysis revealed that the reduction of 10-min and 30-min food intake elicited by each dose of CCK-8 was significantly larger in the apo AIV KO mice than in the WT mice. Peripheral CCK 1 receptor (CCK1R) gene expression (mRNA) in the duodenum and gallbladder of the fasted apo AIV KO mice was comparable to that in WT mice. In contrast, CCK1R mRNA in nodose ganglia of the apo AIV KO mice was upregulated relative to WT animals. Similarly, upregulated CCK1R gene expression was found in the brain stem of apo AIV KO mice by in situ hybridization. Although it is possible that the increased satiating potency of CCK in apo AIV KO mice is mediated by upregulation of CCK 1R in the nodose ganglia and nucleus tractus solitarius, additional experiments are required to confirm such a mechanism.

scholarly journals Reg-II Is an Exocrine Pancreas Injury-Response Product That Is Up-Regulated by Keratin Absence or Mutation

2007 ◽  
Vol 18 (12) ◽  
pp. 4969-4978 ◽  
Author(s):  
Bihui Zhong ◽  
Pavel Strnad ◽  
Diana M. Toivola ◽  
Guo-Zhong Tao ◽  
Xuhuai Ji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Exocrine Pancreas ◽  
Pancreatic Injury ◽  
Recovery Phase ◽  
Wild Type ◽  
Peptide Antibody ◽  
Keratin Filament ◽  
Candidate Protein ◽  
Cytoplasmic Filament

The major keratins in the pancreas and liver are keratins 8 and 18 (K8/K18), but their function seemingly differs in that liver K8/K18 are essential cytoprotective proteins, whereas pancreatic K8/K18 are dispensable. This functional dichotomy raises the hypothesis that K8-null pancreata may undergo compensatory cytoprotective gene expression. We tested this hypothesis by comparing the gene expression profile in pancreata of wild-type and K8-null mice. Most prominent among the up-regulated genes in K8-null pancreas was mRNA for regenerating islet-derived (Reg)-II, which was confirmed by quantitative reverse transcription-polymerase chain reaction and by an anti-Reg-II peptide antibody we generated. Both K8-null and wild-type mice express Reg-II predominantly in acinar cells as determined by in situ hybridization and immunostaining. Analysis of Reg-II expression in various keratin-related transgenic mouse models showed that its induction also occurs in response to keratin cytoplasmic filament collapse, absence, or ablation of K18 Ser52 but not Ser33 phosphorylation via Ser-to-Ala mutation, which represent situations associated with predisposition to liver but not pancreatic injury. In wild-type mice, Reg-II is markedly up-regulated in two established pancreatitis models in response to injury and during the recovery phase. Thus, Reg-II is a likely mouse exocrine pancreas cytoprotective candidate protein whose expression is regulated by keratin filament organization and phosphorylation.

scholarly journals Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis.

1994 ◽  
Vol 127 (6) ◽  
pp. 1717-1727 ◽  
Author(s):  
S Estus ◽  
W J Zaks ◽  
R S Freeman ◽  
M Gruda ◽  
R Bravo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
In Situ Hybridization ◽  
Programmed Cell Death ◽  
Sympathetic Neurons ◽  
Genetic Program ◽  
Nuclear Staining ◽  
Initial Stimulus ◽  
Induced Genes

We have examined the hypothesis that neuronal programmed cell death requires a genetic program; we used a model wherein rat sympathetic neurons maintained in vitro are deprived of NGF and subsequently undergo apoptosis. To evaluate gene expression potentially necessary for this process, we used a PCR-based technique and in situ hybridization; patterns of general gene repression and selective gene induction were identified in NGF-deprived neurons. A temporal cascade of induced genes included "immediate early genes," which were remarkable in that their induction occurred hours after the initial stimulus of NGF removal and the synthesis of some required ongoing protein synthesis. The cascade also included the cell cycle gene c-myb and the genes encoding the extracellular matrix proteases transin and collagenase. Concurrent in situ hybridization and nuclear staining revealed that while c-jun was induced in most neurons, c-fos induction was restricted to neurons undergoing chromatin condensation, a hallmark of apoptosis. To evaluate the functional role of the proteins encoded by these genes, neutralizing antibodies were injected into neurons. Antibodies specific for either c-Jun or the Fos family (c-Fos, Fos B, Fra-1, and Fra-2) protected NGF-deprived neurons from apoptosis, whereas antibodies specific for Jun B, Jun D, or three nonimmune antibody preparations had no protective effect. Because these induced genes encode proteins ranging from a transcription factor necessary for death to proteases likely involved in tissue remodeling concurrent with death, these data may outline a genetic program responsible for neuronal programmed cell death.

Roles of Pax-6 in murine diencephalic development

Development ◽  
1997 ◽  
Vol 124 (8) ◽  
pp. 1573-1582 ◽  
Author(s):  
N. Warren ◽  
D.J. Price
Keyword(s):  
Gene Expression ◽  
Regional Differences ◽  
Third Ventricle ◽  
Regulatory Gene ◽  
Wild Type ◽  
Dorsal Midline ◽  
The Third ◽  
Normal Expression ◽  
In Situ Hybridizations

Pax-6 is one of the earliest regulatory genes to be expressed in the diencephalon. We tested whether normal Pax-6 protein is required for early diencephalic development by examining morphology, precursor proliferation and patterns of regulatory gene expression in the embryonic diencephalon of Small-eye mice (Pax-6 mutants). In Small-eye mice, diencephalic morphology was abnormal at all the embryonic ages studied (days 10.5, 12.5 and 14.5). Regional differences in diencephalic cell density were lost, the diencephalon/mesencephalon boundary was unclear and the third ventricle was enlarged. We estimated diencephalic proliferative rates after labelling with bromodeoxyuridine and found that they were abnormally low in mutants aged embryonic day 10.5. In older mutants, the diencephalon contained fewer cells than normal. In wild-type E14.5 diencephalon, Pax-6, Dlx-2 and Wnt-3 are expressed in discrete regions along the rostrocaudal and dorsoventral axes. In situ hybridizations for these genes in E14.5 Small-eye mice revealed discrete zones of diencephalic expression that had similar relative positions to those in wild-type mice. Some differences of detail in their expression were seen: Pax-6 had an expanded rostral domain of expression and an abnormally indistinct caudal boundary; Dlx-2 had a diffuse, rather than a sharp, caudal boundary of expression; the normally high dorsal midline expression of Wnt-3 was lost. We conclude that normal expression of Pax-6 is required for the correct regulation of diencephalic precursor proliferation. Pax-6 may also control some aspects of diencephalic differentiation, but its mutation in Small-eye mice does not preclude the development of a degree of diencephalic regionalization resembling that in normal mice.

scholarly journals Identification of Genes Particularly Sensitive to Lipopolysaccharide (LPS) in Human Monocytes Induced by Wild-Type versus LPS-Deficient Neisseria meningitidis Strains

2008 ◽  
Vol 76 (6) ◽  
pp. 2685-2695 ◽  
Author(s):  
Reidun Øvstebø ◽  
Ole Kristoffer Olstad ◽  
Berit Brusletto ◽  
Anne Sophie Møller ◽  
Audun Aase ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neisseria Meningitidis ◽  
Differentially Expressed Genes ◽  
Meningococcal Disease ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Type I ◽  
Human Monocytes ◽  
Wild Type ◽  
Inducible Genes

ABSTRACT Lipopolysaccharide (LPS) in the outer membrane of Neisseria meningitidis plays a dominant role as an inflammation-inducing molecule in meningococcal disease. We have used microarray analysis to study the global gene expression after exposure of human monocytes for 3 h to wild-type N. meningitidis (106), LPS-deficient N. meningitidis (106 and 108), and purified N. meningitidis LPS (1 ng [33 endotoxin units]/ml) to identify LPS-inducible genes. Wild-type N. meningitidis (106) induced 4,689 differentially expressed genes, compared with 72 differentially expressed genes induced by 106 LPS-deficient N. meningitidis organisms. However, 108 LPS-deficient N. meningitidis organisms induced 3,905 genes, indicating a dose-response behavior of non-LPS cell wall molecules. A comparison of the gene expression patterns from 106 wild-type N. meningitidis and 108 LPS-deficient N. meningitidis organisms showed that 2,401 genes in human monocytes were not strictly LPS dependent. A list of “particularly LPS-sensitive” genes (2,288), differentially induced by 106 wild-type N. meningitidis but not by 108 LPS-deficient N. meningitidis organisms, showed an early expression of beta interferon (IFN-β), most likely through the Toll-like receptor-MyD88-independent pathway. Subsequently, IFN-β may activate the type I IFN signaling pathway, and an unknown number of IFN-β-inducible genes, such as those for CXCL9, CXCL10, CXCL11, IFIT1, IFIT2, IFIT3, and IFIT5, are transcribed. Supporting this, human monocytes secreted significantly higher levels of CXCL10 and CXCL11 when stimulated by 106 wild-type N. meningitidis organisms than when stimulated by 108 LPS-deficient N. meningitidis organisms. Plasma CXCL10, but not CXCL11, was positively correlated (r = 0.67; P < 0.01) to LPS in patients (n = 24) with systemic meningococcal disease. Thus, new circulating biomarkers in meningococcal disease may be suggested through LPS-induced gene expression changes in human monocytes.

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