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'Complement Receptor Deficiency' (2344)


Feb
2018

Inflammation and immunity play crucial roles in the development of hypertension. Complement activation-mediated innate immune response is involved in the regulation of hypertension and target organ damage. However, whether complement-mediated T cell functions could regulate blood pressure (BP) elevation in hypertension is still unclear.

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Mar
2018

The IgG activities of antigen recognition, Fc-mediated complement activation and cellular Fcγ-receptors (FcγRs) binding are critical for intravenous immunoglobulin (IVIg) immunotherapy in a variety of immune deficiency diseases. Further, these activities could be influenced by different plasma sources and the IVIg manufacturing processes of different manufacturers. This study evaluated and compared the biological activities of IgG in 7 IVIg preparations produced by different Chinese manufacturers.

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Feb
2018

Cell level inflammatory signalling is a combination of initiation at cell membrane receptors and modulation by cytoplasmic regulatory proteins. For keratinocytes, the predominant cell type in the epidermis, this would include toll-like receptors (TLR) and cytoplasmic proteins that propagate or dampen post-receptor signalling. We previously reported that increased levels of tumor necrosis factor α induced protein 3-interacting protein 1 (TNIP1) in HaCaT keratinocytes leads to decreased expression of stress response and inflammation-associated genes.

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Dec
1969

Although the spleen is a major site for West Nile virus (WNV) replication and spread, relatively little is known about which innate cells in the spleen replicate WNV, control viral dissemination, and/or prime innate and adaptive immune responses. Here we tested if splenic macrophages (MΦs) were necessary for control of WNV infection. We selectively depleted splenic MΦs, but not draining lymph node MΦs, by injecting mice intravenously with clodronate liposomes several days prior to infecting them with WNV.

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Dec
2017

Extracts from Salvia miltiorrhiza Bunge have been used in traditional Asian medicine to treat coronary heart disease, chronic renal failure, atherosclerosis, myocardial infraction, angina pectoris, myocardial ischemia, dysmenorrheal, neurasthenic insomnia, liver fibrosis and cirrhosis. The aim of the study was to investigate the anti-RANK signal effect of the combination of S.miltiorrhiza Bunge (SME) and liquefied calcium (LCa) supplement with ovariectomized (OVX-SML) mice, a osteoporosis animal model.

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Dec
2017

In addition to activated T cells, the immune checkpoint inhibitor "V domain-containing Ig suppressor of T-cell activation" (VISTA) is expressed by myeloid cell types, including macrophages and neutrophils. The importance of VISTA expression by myeloid cells to antibody-induced arthritis and its potential for relevance in human disease was evaluated.
VISTA was immunolocalized in normal and arthritic human synovial tissue sections and synovial tissue lysates were subjected to western blot analysis.

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Dec
2017

Hypertension is one of the most common risk factors for the development heart failure in the general population. Inflammation plays a central role in this adverse remodeling and eventually to the development of heart failure. Circulating levels of Complement factor 5a (C5a) are increased in hypertensive patients and the C5a receptor is associated with the presence of cardiac fibrosis and inflammation in an experimental hypertension model.

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Jan
2018

Lack of cell surface glycosylphosphatidylinositol (GPI)-anchored protein(s) has been used as a reporter of Pig-a gene mutation in several model systems. As an extension of this work, our laboratory initiated development of an in vitro mutation assay based on the flow cytometric assessment of CD90.2 expression on the cell surface of the mouse lymphoma cell line L5178Y/Tk.

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Nov
2017

The circadian system regulates numerous physiological processes including immune responses. Here, we show that mice deficient of the circadian clock genesand[double knockout (DKO)] develop an autoimmune phenotype including high serum IgG concentrations, serum antinuclear antibodies, and precipitation of IgG, IgM, and complement 3 in glomeruli and massive infiltration of leukocytes into the lungs and kidneys. Flow cytometry of lymphoid organs revealed decreased pre-B cell numbers and a higher percentage of mature recirculating B cells in the bone marrow, as well as increased numbers of B2 B cells in the peritoneal cavity ofDKO mice.

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Dec
2017

Many complement structures and a number of additional factors, i.e. autoantibodies, receptors, hormones and cytokines, are implicated in the complex pathogenesis of systemic lupus erythematosus.

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Dec
2017

Electronegative low-density lipoprotein (LDL) L5 is a naturally occurring, atherogenic entity found at elevated levels in the plasma of patients with metabolic syndrome (MetS) in the absence of elevated plasma LDL levels.
To investigate the role of L5 in the mechanism of adipose tissue inflammation associated with MetS.
Plasma LDL isolated from patients with MetS (n = 29) and controls (n = 29) with similar plasma LDL levels was separated into five subfractions, L1 to L5, with increasing electronegativity.

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Oct
2017

Sepsis is an infection-induced systemic inflammatory syndrome and a major cause of death for critically ill patients. Here, we examined whether the absence of Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, influences host defense against polymicrobial sepsis (PMS) induced by cecal ligation and puncture (CLP). Compared to wild-type mice, Spred2mice exhibited higher survival rates with increased level of leukocyte infiltration and local chemokine production and reduced plasma and peritoneal bacterial loads after CLP.

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Dec
1969

Hereditary angioedema (HAE) with C1 inhibitor deficiency is a genetic disorder that clinically manifests with attacks of angioedema in the subcutaneous and submucosal tissues, mainly in the extremities, abdomen, and upper airway. During attacks, vascular permeability is increased due to increased bradykinin (BK). This means that special therapies are needed for attacks that do not respond to traditional antiallergic therapies involving antihistamines, corticosteroids, and epinephrine.

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Dec
1969

Complement factor C5a has two known receptors, C5aR, which mediates proinflammatory effects, and C5L2, a potential C5a decoy receptor. We previously identified C5a/C5aR signaling as a potent profibrotic pathway in the kidney. Here we tested for the first time the role of C5L2 in renal fibrosis.

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Dec
1969

Neutrophils and macrophages are important constituents of the hepatic inflammatory infiltrate in non-alcoholic steatohepatitis. These innate immune cells express CD18, an adhesion molecule that facilitates leukocyte activation. In the context of fatty liver, activation of infiltrated leukocytes is believed to enhance hepatocellular injury.

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Aug
2017

As a β2 integrin family member, Mac-1 plays an important role in the inflammatory response. Inflammation and lung injury are closely associated, but the involvement of Mac-1 in the occurrence and development of such pathologies remains poorly understood. We aimed to investigate the relationship between Mac-1 deficiency and respiratory failure in Mac-1 knockout {Mac-1} mice, using C57BL/6J mice as a control.

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Feb
2018

In obesity, B cells accumulate in white adipose tissue (WAT) and produce IgG, which may contribute to the development of glucose intolerance. IgG signals by binding to Fcγ receptors (FcγR) and by activating the complement system. The aim of our study was to investigate whether activation of FcγR and/or complement C3 mediates the development of high-fat diet-induced glucose intolerance.

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Dec
2017

Interleukin 17A (IL-17A) and complement (C') activation have each been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We have reported that IL-17A induces epithelial injuryTGF-β in murine bronchiolitis obliterans; that TGF-β and the C' cascade present signaling interactions in mediating epithelial injury; and that the blockade of C' receptors mitigates lung fibrosis. In the present study, we investigated the role of IL-17A in regulating C' in lung fibrosis.

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Dec
1969

CCRL2 is a 7-transmembrane domain receptor that shares structural and functional similarities with the family of atypical chemokine receptors (ACKRs). CCRL2 is upregulated by inflammatory signals and, unlike other ACKRs, it is not a chemoattractant-scavenging receptor, does not activate β-arrestins, and is widely expressed by many leukocyte subsets. Therefore, the biological role of CCRL2 in immunity is still unclear.

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Dec
2017

Seizures are due to excessive, synchronous neuronal firing in the brain and are characteristic of epilepsy, the fourth most prevalent neurological disease. We report handling-induced and spontaneous seizures in mice deficient for CD39, a cell-surface ATPase highly expressed on microglial cells. CD39mice with handling-induced seizures had normal input-output curves and paired-pulse ratio measured from hippocampal slices and lacked microgliosis, astrogliosis or overt cell loss in the hippocampus and cortex.

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Dec
1969

Our group previously investigated the levels of anti-Gal and anti-nonGal IgM and IgG in a cohort of 75 healthy humans of various backgrounds, and found some significant differences related to factors such as age, gender, ABO blood group, diet, vaccination history, and geographic location during childhood. We have now expanded our cohort (n = 84) to investigate the levels of anti-Neu5Gc and anti-nonGal/nonNeu5Gc antibodies in healthy humans. Anti-nonGal and anti-nonGal/nonNeu5Gc human IgM and IgG binding to pRBCs and pAECs from GTKO/CD46 and GTKO/CD46/Neu5GcKO pigs were measured by flow cytometry.

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Jan
2018

Thyroid hormones regulate many aspects of brain development and function, and alterations in the levels of thyroid hormone action lead to abnormal anxiety- and depression-like behaviors. A complement of factors in the brain function independently of circulating levels of hormone to strictly controlled local thyroid hormone signaling. A critical factor is the type 3 deiodinase (DIO3), which is located in neurons and protects the brain from excessive thyroid hormone.

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Dec
1969

Transplant-associated thrombotic microangiopathy (TA-TMA) is a common and poorly recognized complication of hematopoietic stem cell transplantation (HSCT) associated with excessive complement activation, likely triggered by endothelial injury. An important missing piece is the link between endothelial injury and complement activation. We hypothesized that neutrophil extracellular traps (NETs) mechanistically link endothelial damage with complement activation and subsequent TA-TMA.

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Sep
2017

Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis) promotes lesion growth and establishment of a necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is an important modulator of myeloid function and programming.

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Dec
1969

CD11cdendritic cells (DCs) exert a critical role as antigen-presenting cells in regulating pathogenic T cells in multiple sclerosis (MS). To determine whether the therapeutic benefit of interferon-β (IFN-β) treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN-βand IFN-βmice using a myelin oligodendrocyte glycoprotein (MOG) peptide-induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our earlier work identified that IFN-βmice exhibit earlier onset and more rapid progression of neurological impairment compared with IFN-βmice.

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Dec
1969

Coix seed has the functions of fortifying the spleen and inhibiting the dampness. However, it remains unclear which Coix seed compositions is responsible for these functions. Previous investigations have revealed that the main compositions of Coix seed are proteins, polysaccharides, oils and starches.

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Dec
1969

Fluid-phase pinocytosis is a receptor-independent mechanism of endocytosis that occurs in all mammalian cells and may be a mechanism for the uptake of LDL by macrophages. As there are currently no methods for the measurement of fluid-phase pinocytosis by individual aortic cells in vivo, we sought to identify a suitable method.
ApoE-/- mice were retro-orbitally injected with AngioSPARK fluorescent nanoparticles specifically designed to not interact with cells.

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Dec
1969

Gene knockout mice of glycosyltransferases have clearly showed roles of their products in the bodies, while there are examples where phenotype of knockout was much less severe than expected probably due to functional redundancy. The most striking novel finding obtained from ganglioside-deficient mice was that progressive inflammatory reaction took place, leading to neurodegeneration. In particular, dysfunction of complement-regulatory proteins due to deteriorated architecture of lipid rafts seemed to be essential mechanisms for the inflammation.

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Sep
2017

Regeneration and repair mediated by mesenchymal stem cells (MSCs) are key self-protection mechanisms against diabetic complications, a reflection of diabetes-related cell/tissue damage and dysfunction. MSC abnormalities have been reported during the progression of diabetic complications, but little is known about whether a deficiency in these cells plays a role in the pathogenesis of this disease. In addition to MSC resident sites, peripheral circulation is a major source of MSCs that participate in the regeneration and repair of damaged tissue.

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Aug
2017

We have recently demonstrated that disruption of the murine cytochrome-450 2c44 gene (exacerbates chronic hypoxia-induced pulmonary artery remodeling and hypertension in mice. Subsequently, we serendipitously found thatgene disruption also increases hematopoietic stem cell (HSC) numbers in bone marrow and blood. Therefore, the objective of the present study was to investigate whether CYP2C44-derived eicosanoids regulate HSC proliferation/cell growth and whether increased HSCs contribute to chronic hypoxia-induced remodeling of pulmonary arteries inknockout mice.

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Jan
2018

Leukocyte-adhesion deficiency-1 is a recessively inherited disorder associated with recurrent bacterial infections, severe periodontitis, peripheral leukocytosis, and impaired wound healing. We diagnosed moderate-type leukocyte-adhesion deficiency-1 in a 7-year-old girl who developed a necrotizing ulcer after Bacillus Calmette-Guerin vaccination. The patient showed moderate expression of CD18 in neutrophils with a homozygous splice mutation with c.

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Dec
1969

Macrophage accumulation is a critical step during development of chronic inflammation, initiating progression of many devastating diseases. Leukocyte-specific integrin αβ(CD11d/CD18) is dramatically upregulated on macrophages at inflammatory sites. Previously we found that CD11d overexpression on cell surfaces inhibits in vitro cell migration due to excessive adhesion.

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Dec
1969

Elderly with late-onset recurrent respiratory tract infections (RRTI) often have specific anti-polysaccharide antibody deficiency (SPAD). We hypothesized that late-onset RRTI is caused by mild immunodeficiencies, such as SPAD, that remain hidden through adult life. We analyzed seventeen elderly RRTI patients and matched controls.

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Jul
2017

Concentrated fish oils, containing a mixture of long-chain monounsaturated fatty acids (LCMUFA) with aliphatic chains longer than 18 C atoms (i.e., C20:1 and C22:1), have been shown to attenuate atherosclerosis development in mouse models.

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Dec
2017

Although amyloid β peptide (Aβ) is cleared from the brain to cerebrospinal fluid and the peripheral circulation, mechanisms for its removal from blood remain unresolved. Primates have uniquely evolved a highly effective peripheral clearance mechanism for pathogens, immune adherence, in which erythrocyte complement receptor 1 (CR1) plays a major role.
Multidisciplinary methods were used to demonstrate immune adherence capture of Aβ by erythrocytes and its deficiency in Alzheimer's disease (AD).

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Dec
1969

IFN-γ-producing T helper 1 (Th1) cell responses mediate protection against infections but uncontrolled Th1 activity also contributes to a broad range of autoimmune diseases. Autocrine complement activation has recently emerged as key in the induction and contraction of human Th1 immunity: activation of the complement regulator CD46 and the C3aR expressed by CD4T cells via autocrine generated ligands C3b and C3a, respectively, are critical to IFN-γ production. Further, CD46-mediated signals also induce co-expression of immunosuppressive IL-10 in Th1 cells and transition into a (self)-regulating and contracting phase.

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Dec
1969

Dendritic cells (DCs) are specialized in Ag engulfment via a wide variety of uptake receptors on their cell surface. In the present study we investigated Ag uptake and presentation of in vivo-formed Ag-Ab complexes by i.v.

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Dec
1969

α-haemolysin (HlyA)-producingcommonly inflict severe urinary tract infections, including pyelonephritis, which comprises substantial risk for sepsis., the cytolytic effect of HlyA is mainly mediated by ATP release through the HlyA pore and subsequent P2X/P2Xreceptor activation. This amplification of the lytic process is not unique to HlyA but is observed by many other pore-forming proteins including complement-induced haemolysis.

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Apr
2017

HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects.
We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR) mice fed a high-cholesterol diet for 13 weeks.

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Dec
1969

Aquaporin-4 (AQP4), a key molecule for water homeostasis in the brain, is associated with adult neurogenesis, but its mechanisms regulating adult neural stem cells (aNSC) remain largely unexplored. Neuroinflammation has a relevant influence on adult neurogenesis, which is a common feature in various neurodegenerative diseases. Considering the possible link between neuroinflammation and AQP4, we speculate that AQP4 may mediate the synthesis and release of proinflammatory cytokines in glia and then indirectly regulate adult hippocampal neurogenesis.

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Dec
1969

Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo, suggesting that blockade of the SIRPα-CD47 checkpoint could be useful in treating human cancer.

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Dec
1969

The complement system, and specifically C5a, is involved in renal ischemia-reperfusion (IR) injury. The 2 receptors for complement anaphylatoxin C5a (C5aR1 and C5aR2) are expressed on leukocytes as well as on renal epithelium. Extensive evidence shows that C5aR1 inhibition protects kidneys from IR injury; however, the role of C5aR2 in IR injury is less clear as initial studies proposed the hypothesis that C5aR2 functions as a decoy receptor.

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Dec
1969

Skin inflammation induced by lupus serum is a useful tool to investigate the pathogenesis of lupus skin injury. IL-1 is a proinflammatory cytokine, and its role in lupus skin lesion is still unclear. We determined the role of IL-1 in lupus skin injury by using gene deficient mice.

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Mar
2017

In a longitudinal study including 642 healthy 8-11-year-old Danish children, we investigated associations between vitamin D dependent SNP and serum 25-hydroxyvitamin D (25(OH)D) concentrations across a school year (August-June). Serum 25(OH)D was measured three times for every child, which approximated measurements in three seasons (autumn, winter, spring). Dietary and supplement intake, physical activity, BMI and parathyroid hormone were likewise measured at each time point.

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Dec
1969

Both variants affecting splice sites and those in splicing regulatory elements (SREs) can impair pre-mRNA splicing, eventually leading to severe diseases. Despite the availability of many prediction tools, prognosis of splicing affection is not trivial, especially when SREs are involved. Here, we present data on 92 in silico-/55 minigene-analysed variants detected in genes responsible for the primary immunodeficiencies development (namely BTK, CD40LG, IL2RG, SERPING1, STAT3, and WAS).

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Dec
1969

Th17 cells play a critical role in autoimmune diseases, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Response gene to complement (RGC)-32 is a cell cycle regulator and a downstream target of TGF-β that mediates its profibrotic activity. In this study, we report that RGC-32 is preferentially upregulated during Th17 cell differentiation.

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Dec
1969

β-Thalassemia is associated with several abnormalities of the innate immune system. Neutrophils in particular are defective, predisposing patients to life-threatening bacterial infections. The molecular and cellular mechanisms involved in impaired neutrophil function remain incompletely defined.

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Mar
2017

Evidence from mice suggests that brain infiltrating immune cells contribute to neurodegeneration, and we previously identified a deleterious lymphocyte infiltration in Parkinson's disease mice. However, this remains controversial for monocytes, due to artifact-prone techniques used to distinguish them from microglia. Our aim was to reassess this open question, by taking advantage of the recent recognition that chemokine receptors CCR2 and CX3CR1 can differentiate between inflammatory monocytes and microglia, enabling to test whether CCR2monocytes infiltrate the brain during dopaminergic (DA) neurodegeneration and whether they contribute to neuronal death.

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Mar
2017

CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage, but the involvement in this neuroprotective effect of the various C/EBPβ-expressing cell types is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture, we hypothesized that specific C/EBPβ deficiency in microglia could be neuroprotective in vivo.

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