)| PMID |
14960605 ( ) |
|---|---|
| Title | Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis. |
| Abstract | Innate immunity is a specific and organized immunological program engaged by peripheral organs and the CNS to maintain homeostasis after stress and injury. In neurodegenerative disorders, its putative deregulation, featured by inflammation and activation of glial cells resulting from inherited mutations or viral/bacterial infections, likely contributes to neuronal death. However, it remains unclear to what extent environmental factors and innate immunity cooperate to modulate the interactions between the neuronal and non-neuronal elements in the perturbed CNS. In the present study, we addressed the effects of acute and chronic administration of lipopolysaccharide (LPS), a Gram-negative bacterial wall component, in a genetic model of neurodegeneration. Transgenic mice expressing a mutant form of the superoxide dismutase 1 (SOD1(G37R)) linked to familial amyotrophic lateral sclerosis were challenged intraperitoneally with a single nontoxic or repeated injections of LPS (1 mg/kg). At different ages, SOD1(G37R) mice responded normally to acute endotoxemia. Remarkably, only a chronic challenge with LPS in presymptomatic 6-month-old SOD1(G37R) mice exacerbated disease progression by 3 weeks and motor axon degeneration. Closely associated with the severity of disease is the stronger and restricted upregulation of the receptor of innate immunity Toll-like receptor 2 and proinflammatory cytokines in degenerating regions of the ventral spinal cord and efferent fiber tracts of the brain from the LPS-treated SOD1(G37R) mice. This robust immune response was not accompanied by the establishment of acquired immunity. Our results provide solid evidence that environmental factors and innate immunity can cooperate to influence the course of disease of an inherited neuropathology. McGill University, The Montreal General Hospital Research Institute, Montreal, Quebec H3G 1A4, Canada. Neuroscience |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 108 | superoxide dismutase 1 | SOD1 | hSOD1 | SOD1s | mSOD1 | |
| 11848 | TLR2 | toll-like receptor 2 | 22 | toll like receptor 2 | TLR2 | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 18 | tumor necrosis factor alpha | TNF-alpha | tnf alpha | |
| 5438 | IFNG | interferon, gamma | 5 | IFN-gamma | interferon gamma | |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | 3 | FasL | fas ligand | |
| 7685 | NDUFA2 | NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8kDa | 2 | CD14 | |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | 2 | NF-kappaB | |
| 4931 | HLA-A | major histocompatibility complex, class I, A | 2 | MHC | |
| 18809 | TUBA1B | tubulin, alpha 1b | 2 | alpha tubulin | |
| 1774 | CDK5 | cyclin-dependent kinase 5 | 2 | cyclin dependent kinase 5 | Cdk5 | |
| 1678 | CD4 | CD4 molecule | 2 | CD4 | |
| 1706 | CD8A | CD8a molecule | 1 | CD8 | |
| 11850 | TLR4 | toll-like receptor 4 | 1 | TLR4 | |
| 352 | AIF1 | allograft inflammatory factor 1 | 1 | iba1 | |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | 1 | Fas | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | expressing a mutant form of the superoxide dismutase 1 (SOD1 SOD1 linked to familial amyotrophic lateral sclerosis were challenged intraperitoneally with |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | At different ages SOD1 mice responded normally to acute endotoxemia |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Remarkably only a chronic challenge with LPS in presymptomatic 6-month-old SOD1 mice exacerbated disease progression by 3 weeks and motor axon |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | and efferent fiber tracts of the brain from the LPS-treated SOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | mice expressing a mutant form of superoxide dismutase 1 (SOD1 SOD1 linked to amyotrophic lateral sclerosis (ALS), ALS the most common |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | The SOD1 protein is a cytosolic metalloenzyme catalyzing the conversion of superoxide |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Transgenic mice expressing mutant SOD1 develop motor neuron disease resembling ALS through a gain of |
| 11920 | FAS | Fas (TNF receptor superfamily, member 6) | Fas | 0.6 | et al. 1998 cytoskeletal abnormalities (Wong Wong et al. 1995 Fas ligand (FasL)-mediated FasL -mediated death (Raoul Raoul et al. 2002 |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | FasL | 2.2 | cytoskeletal abnormalities (Wong Wong et al. 1995 Fas ligand (FasL)-mediated FasL -mediated death (Raoul Raoul et al. 2002 and deregulation of |
| 1774 | CDK5 | cyclin-dependent kinase 5 | Cdk5 | 1.9 | -mediated death (Raoul Raoul et al. 2002 and deregulation of Cdk5 (cyclin-dependent cyclin-dependent kinase 5 (Nguyen Nguyen et al. 2001a |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Despite these findings the toxicity of SOD1 mutants linked to human ALS remains poorly understood |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | SOD1 is a ubiquitously expressed protein and therefore it is possible |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Indeed a restricted expression of mutant SOD1 to neurons in transgenic mice was not sufficient to provoke |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Neither did the selective expression of mutant SOD1 in astrocytes provoke pathology despite astrocytosis (Gong Gong et al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | In the present study we triggered the innate immunity of SOD1 mice with systemic administration of lipopolysaccharide (LPS), LPS a potent |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | immunity by systemic LPS is noxious to motor neurons bearing SOD1 linked to ALS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Generation of SOD1 mice and protocol for LPS injection |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | The inbred C57BL/6 C57BL 6 SOD1 mice (line line 29 used in this study have a |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | C57BL/6 C57BL 6 SOD1 mice (line line 42 exhibit a life span of 5-6 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | The SOD1 mice were housed at room temperature (21degreeC) 21degreeC and in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | immune response in the CNS presymptomatic 3- 6- and 9-month-old SOD1 mice received a single intraperitoneal injection of LPS (1 1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Another group of presymptomatic 6-month-old SOD1 mice received intraperitoneal LPS or vehicle injections once every 2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | month 9 (42-43 42-43 weeks of age the chronically LPS-treated SOD1 mice exhibited the first signs of paralysis and the injections |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | At the same time Veh-SOD1 or SOD1 mice that did not show signs of paralysis were killed |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Some of the Veh-SOD1 or SOD1 were left until they exhibited the paralytic phenotype (3-5 3-5 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Thus the analysis of the Veh-SOD1 and SOD1 mice was performed strictly before the onset and not at |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | SOD1 mice exhibited a normal innate immune response after an acute |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | and spinal cord of both normal wild-type (WT)] WT and SOD1 mice ( Fig 1 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | et al. 2001 kappaB alpha inhibitory protein of nuclear factor-kappaB NF-kappaB (index index of NF-kappaB activity tumor necrosis factor-alpha TNF-alpha and |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.6 | alpha inhibitory protein of nuclear factor-kappaB NF-kappaB (index index of NF-kappaB activity tumor necrosis factor-alpha TNF-alpha and CD14 (data data not |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | factor-kappaB NF-kappaB (index index of NF-kappaB activity tumor necrosis factor-alpha TNF-alpha and CD14 (data data not shown |
| 7685 | NDUFA2 | NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8kDa | CD14 | 1.0 | (index index of NF-kappaB activity tumor necrosis factor-alpha TNF-alpha and CD14 (data data not shown |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | Activation of innate immunity featured by the expression of TLR2 and several other inflammatory genes takes place in transgenic mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | several other inflammatory genes takes place in transgenic mice expressing SOD1 linked to ALS (Nguyen Nguyen et al. 2001b |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | the pathogenesis and neuronal death processes of ALS caused by SOD1 mutation |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Although SOD1 mice responded normally to an acute systemic injection of LPS |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | the bacterial cell wall component led to sustained induction of TLR2 receptor strictly within parenchymal microglial cells |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | This upregulation of TLR2 was not accompanied by enhanced expression of both endogenous and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | not accompanied by enhanced expression of both endogenous and transgene SOD1 ( Fig 6 |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | Most importantly the degree of TLR2 induction correlated perfectly with degenerating motor neurons and motor axons |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | As a consequence the chronically LPS-treated SOD1 mice exhibited accelerated disease progression motor axon degeneration and a |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Interestingly chronically LPS-treated SOD1 mice exhibited a more important loss of astrocytes than Veh-treated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | a more important loss of astrocytes than Veh-treated or nontreated SOD1 mice |
| 7685 | NDUFA2 | NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8kDa | CD14 | 1.0 | microglia because these cells are of myeloid lineage and express CD14 and TLR4 receptors (Lacroix Lacroix et al. 1998 gamma (Moser |
| 11850 | TLR4 | toll-like receptor 4 | TLR4 | 1.6 | these cells are of myeloid lineage and express CD14 and TLR4 receptors (Lacroix Lacroix et al. 1998 gamma (Moser Moser and |
| 4931 | HLA-A | major histocompatibility complex, class I, A | MHC | 1.5 | molecules of adaptive immunity such as major histocompatibility complex (MHC) MHC class I MHC class II and human histocompatibility leukocyte antigen |
| 4931 | HLA-A | major histocompatibility complex, class I, A | MHC | 1.5 | immunity such as major histocompatibility complex (MHC) MHC class I MHC class II and human histocompatibility leukocyte antigen in brains spinal |
| 5438 | IFNG | interferon, gamma | IFN-gamma | 1.1 | tissue of these animals did not exhibit positive signal for IFN-gamma transcript |
| 1678 | CD4 | CD4 molecule | CD4 | 0.3 | Immunohistochemistry also failed to detect infiltrating CD4 and CD8 cells in the brain and spinal cord of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | and CD8 cells in the brain and spinal cord of SOD1 mice treated chronically with vehicle or LPS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | response may be toxic for the CNS of the LPS-treated SOD1 and SOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | response may be toxic for the CNS of the LPS-treated SOD1 and SOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | be toxic for the CNS of the LPS-treated SOD1 and SOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | For instance upregulation of the local adaptive immune response in SOD1 mice with Copaxone (glatiramer glatiramer acetate vaccination eliminates destructive self-compounds |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | The proapoptotic cytokine TNF-alpha is likely to play a determinant role in this model |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | is able to trigger transcriptional activation of the gene encoding TNF-alpha in microglial cells across the CNS and TNF-alpha gene expression |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | gene encoding TNF-alpha in microglial cells across the CNS and TNF-alpha gene expression progressively increased in the spinal cord of SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | TNF-alpha gene expression progressively increased in the spinal cord of SOD1 mice (Nadeau Nadeau and Rivest 2000 alpha levels are also |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | FasL | 2.2 | immune response (Nguyen Nguyen et al. 2002 alpha TNFRI TNFRII FasL and FasR will be essential to clarify the roles of |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | In addition determining the endogenous ligand of TLR2 would help in deciphering the mechanistic details of its actions |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | the toxicity of chronic administration of LPS in the mutant SOD1 mice our study constitutes a simple example of genetic modulation |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | Effect of a single bolus of LPS on TLR2 gene expression in the brains and spinal cords of SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | TLR2 gene expression in the brains and spinal cords of SOD1 mice and their WT littermates |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | (BF) BF and dark-field photomicrographs depict the expression pattern of TLR2 mRNA 24 hr after a single intraperitoneal injection of vehicle |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | Coronal and longitudinal sections were hybridized using a mouse TLR2 cRNA probe and dipped into NTB2 emulsion milk |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | within the brain and spinal cord of both WT and SOD1 mice that received an intraperitoneal bolus of LPS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | endotoxin LPS increases the innate immune response and neurodegeneration in SOD1 mice |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | dark-field photomicrographs depict representative examples of the hybridization signal for TNF-alpha ( B IL-12 ( C and TLR2 ( D mRNA |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | hybridization signal for TNF-alpha ( B IL-12 ( C and TLR2 ( D mRNA in the reticular formation just above the |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | interest to note that the hybridization signal for IL-12 and TLR2 overlaps with the fluorochrome FJB ( C D vs E |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | depict examples of microglial cells containing positive hybridization signal for TLR2 mRNA in the reticular formation |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | TLR2 mRNA was thereafter hybridized on the same sections by means |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | Note the presence of the mRNA encoding TLR2 within parenchymal microglia (agglomeration agglomeration of silver grains within the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Exacerbation of motor axon degeneration in chronically LPS-treated SOD1 mice accelerates disease progression |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | A Survival curves of transgenic mice expressing SOD1 challenged systemically with LPS or vehicle every 2 weeks |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | with vehicle (WT-Veh) WT-Veh or LPS (WT-LPS) WT-LPS and from SOD1 mice challenged chronically with vehicle (G37R-Veh) G37R-Veh or LPS (G37R-LPS) |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Robust inflammatory response in ventral spinal horn of chronically LPS-treated SOD1 mice associated with massive degeneration of astrocytes |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | dark-field photomicrographs depict representative examples of the hybridization signal for TNF-alpha IL-12 and TLR2 mRNA in the L5 segment of the |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | representative examples of the hybridization signal for TNF-alpha IL-12 and TLR2 mRNA in the L5 segment of the spinal cord ( |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | Here also the hybridization signal for IL-12 and TLR2 overlaps with the fluorochrome FJB |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | neurons and astrocytes in this region of spinal cord from SOD1 mice |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | Relative expression levels of TLR2 hybridization signal in the brains of SOD1 mice and their |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | expression levels of TLR2 hybridization signal in the brains of SOD1 mice and their wild-type littermates that received chronic systemic injections |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Acute and chronic administration of LPS in SOD1 failed to alter expression of endogenous and transgene SOD1 Six-month-old |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | in SOD1 failed to alter expression of endogenous and transgene SOD1 Six-month-old WT and transgenic SOD1 littermates were analyzed for SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | expression of endogenous and transgene SOD1 Six-month-old WT and transgenic SOD1 littermates were analyzed for SOD1 levels 24 hr after acute |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | SOD1 Six-month-old WT and transgenic SOD1 littermates were analyzed for SOD1 levels 24 hr after acute injection of LPS (1 1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | Expression of both endogenous mSOD1 and hSOD1 remained unaffected in spinal cord ( A lanes |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 1.7 | Expression of both endogenous mSOD1 and hSOD1 remained unaffected in spinal cord ( A lanes 5-8 and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | A lanes 5-8 and spleen ( B lanes 5-8 of SOD1 animals in response to saline (Veh) Veh or LPS injection |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | injection as detected by means of an antibody recognizing both SOD1 proteins |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | The endotoxin also failed to significantly upregulate mSOD1 expression in WT animals ( A B lanes 1-4 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1s | 1.7 | Similar levels of both SOD1s were found in WT and SOD1 mice 48 hr after |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Similar levels of both SOD1s were found in WT and SOD1 mice 48 hr after LPS or Veh administration (data data |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | In SOD1 mice that were chronically treated with LPS expression of mutant |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | mice that were chronically treated with LPS expression of mutant SOD1 (detected detected with an antibody directed against the human transgene |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Lysates from SOD1 line 42 (L42) L42 overexpressing 2- to 2.5-fold the levels |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Thus neither acute nor chronic administration of LPS in SOD1 mice affected expression of endogenous and transgene SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | LPS in SOD1 mice affected expression of endogenous and transgene SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Membranes were incubated with antibodies against SOD1 (Biodesign; Biodesign Santa Cruz Biotechnology Santa Cruz CA alpha-tubulin (B512; |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | Semiquantitative analyses revealed similar increases in expression levels of TLR2 mRNA in different regions of the CNS in both WT |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | in different regions of the CNS in both WT and SOD1 groups of mice challenged acutely with LPS ( Fig 1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | area postrema (AP) AP and spinal L5 segment of LPS-treated SOD1 mice did not exhibit a different hybridization signal when compared |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | These results indicate that SOD1 are not more sensitive to the endotoxin and therefore exhibit |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | of LPS exacerbate disease progression and motor axon degeneration in SOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | injection of an equal dose of LPS in presymptomatic 6-month-old SOD1 mice had a significant effect on their life span |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Figure 2 A shows the survival curve of SOD1 mice (line line 29 treated chronically with Veh or LPS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | The SOD1 mice treated with vehicle ( n = 16 used as |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | is not different from the life span of the nontreated SOD1 mice (Nguyen Nguyen et al. 2000 2001a |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | SOD1 mice treated chronically with LPS ( n = 13 exhibited |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | injections of a nontoxic dose of LPS in presymptomatic 6-month-old SOD1 mice exacerbated disease progression by 3 weeks |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | counted the number of axons in L5 ventral roots of SOD1 mice treated chronically with LPS or vehicle and killed at |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | At this age the L5 ventral roots of LPS-treated SOD1 mice were smaller when compared with those dissected from Veh-SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Furthermore LPS-treated SOD1 mice ( n = 5 had 358 _amp_#177 48 axons |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | n = 5 had 358 _amp_#177 48 axons whereas Veh-treated SOD1 mice ( n = 4 had 478 _amp_#177 40 ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | there was a more severe loss of motor axons in SOD1 mice that received repeated injections with the endotoxin |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | assessed the transcriptional activation of the receptor of innate immunity TLR2 and the proapoptotic cytokine TNF-alpha in the SOD1 mice challenged |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | the receptor of innate immunity TLR2 and the proapoptotic cytokine TNF-alpha in the SOD1 mice challenged chronically with LPS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | innate immunity TLR2 and the proapoptotic cytokine TNF-alpha in the SOD1 mice challenged chronically with LPS |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | TLR2 is induced during disease progression of SOD1 mice and especially |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | TLR2 is induced during disease progression of SOD1 mice and especially in late stages where massive neurodegeneration occurs |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | Similarly a chronic expression of TLR2 might also trigger microglial apoptosis and thereby prevent the detrimental |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | innate immune response was much more pronounced in chronically LPS-treated SOD1 mice than in Veh-treated SOD1 mice (Figs Figs 3 4 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | more pronounced in chronically LPS-treated SOD1 mice than in Veh-treated SOD1 mice (Figs Figs 3 4 5 |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 5.1 | The robust expression of TLR2 mRNA ( Fig 3 D G is associated with strong |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | strong hybridization signals for the genes encoding the proapoptotic cytokines TNF-alpha andinterleukin-12 (IL-12) IL-12 in degenerating efferent fiber tracts of the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | were found in the spinal cord of chronically LPS-treated mutant SOD1 mice ( Fig 4 B |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Absence of adaptive immunity in the CNS of LPS-treated SOD1 mice |
| 5438 | IFNG | interferon, gamma | IFN-gamma | 1.1 | cord and brain tissues using highly sensitive probes for interferon-gamma IFN-gamma and IL-12 two cytokines essential for the transfer from the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | of IL-12 in degenerating CNS regions of the chronically LPS-treated SOD1 mice when compared with chronically Veh-treated SOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | the chronically LPS-treated SOD1 mice when compared with chronically Veh-treated SOD1 mice |
| 5438 | IFNG | interferon, gamma | IFN-gamma | 1.1 | However in situ hybridization failed to detect positive signal for IFN-gamma transcript in the brain and spinal cord of SOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | for IFN-gamma transcript in the brain and spinal cord of SOD1 mice treated acutely or chronically with the endotoxin |
| 1678 | CD4 | CD4 molecule | CD4 | 0.3 | Immunohistochemistry using antibodies directed against CD4 or CD8 also failed to provide anatomical evidence of infiltrating |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | T cells in the CNS of both vehicle- and LPS-treated SOD1 mice (data data not shown |
| 1706 | CD8A | CD8a molecule | CD8 | 0.1 | Immunohistochemistry using antibodies directed against CD4 or CD8 also failed to provide anatomical evidence of infiltrating T cells |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Accelerated neurodegeneration in chronically LPS-treated SOD1 mice is not attributable to an upregulation in levels of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Emerging evidence indicates that LPS can induce SOD1 which subsequently might play an important role in mediating the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | the understanding of mechanisms causing accelerated neurodegeneration in chronically LPS-treated SOD1 mice is whether LPS upregulates expression of the transgene SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | SOD1 mice is whether LPS upregulates expression of the transgene SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | Indeed transgenic mice having higher levels of SOD1 (line line 42 exhibit a more aggressive pathology with previous |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | To address this question protein levels for both endogenous mouse SOD1 (mSOD1) mSOD1 and human mutant SOD1 (hSOD1) hSOD1 were determined |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | this question protein levels for both endogenous mouse SOD1 (mSOD1) mSOD1 and human mutant SOD1 (hSOD1) hSOD1 were determined in SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | for both endogenous mouse SOD1 (mSOD1) mSOD1 and human mutant SOD1 (hSOD1) hSOD1 were determined in SOD1 mice in response to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 1.7 | endogenous mouse SOD1 (mSOD1) mSOD1 and human mutant SOD1 (hSOD1) hSOD1 were determined in SOD1 mice in response to acute or |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | mSOD1 and human mutant SOD1 (hSOD1) hSOD1 were determined in SOD1 mice in response to acute or chronic injection of LPS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | As shown in Figure 6 mSOD1 and hSOD1 levels in spinal cord and spleen were unchanged |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 1.7 | As shown in Figure 6 mSOD1 and hSOD1 levels in spinal cord and spleen were unchanged 24 hr |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | In addition SOD1 mice chronically challenged with LPS did not display increased levels |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | caused by chronic LPS treatment is not caused by enhanced SOD1 expression |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.0 | San Diego La Jolla CA for the kind gift of SOD1 mice (line line 29 Dr Y Imai (National National Institute |
| 352 | AIF1 | allograft inflammatory factor 1 | iba1 | 1.3 | Institute of Neuroscience Kodaira Tokyo Japan for the gift of iba1 antisera Dr A Israel (Institut Institut Pasteur Paris France for |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 1.7 | al Qu_amp_eacute bec Canada for the plasmid containing the mouse TNF-alpha cDNA Dr I Campbell (The The Scripps Research Institute La |
| 5438 | IFNG | interferon, gamma | IFN-gamma | 1.1 | The Scripps Research Institute La Jolla CA for the mouse IFN-gamma cDNA Dr K Pahan (University University of Nebraska Lincoln NE |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | transgenic mice expressing a mutant form of the superoxide dismutase 1 sod1 linked to familial amyotrophic lateral sclerosis were challenged intraperitoneally with a single nontoxic or repeated injections of lps 1 mg/kg . |
| 11848 | TLR2 | toll-like receptor 2 | toll like receptor 2 | 1.0 | closely associated with the severity of disease is the stronger and restricted upregulation of the receptor of innate immunity toll like receptor 2 and proinflammatory cytokines in degenerating regions of the ventral spinal cord and efferent fiber tracts of the brain from the lps treated sod1 mice. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | key words: innate immunity ; neurodegeneration ; lipopolysaccharide ; microglia ; amyotrophic lateral sclerosis ; superoxide dismutase 1 ; proinflammatory cytokines ; transgenic mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | interestingly numerous proinflammatory genes are induced in the cns of presymptomatic mice expressing a mutant form of superoxide dismutase 1 sod1 linked to amyotrophic lateral sclerosis als the most common form of human motor neuron disease nguyen et al. 2001b ~20% cases of familial als rosen et al. 1993 ; cudkowicz et al. 1997 . |
| 1774 | CDK5 | cyclin-dependent kinase 5 | cyclin dependent kinase 5 | 1.0 | 1997 disruption of the calcium homeostasis morrison et al. 1996 ; roy et al. 1998 cytoskeletal abnormalities wong et al. 1995 fas ligand fasl mediated death raoul et al. 2002 and deregulation of cdk5 cyclin dependent kinase 5 nguyen et al. 2001a . |
| 11936 | FASLG | Fas ligand (TNF superfamily, member 6) | fas ligand | 1.0 | posed to account for such toxicity including excitotoxicity bruijn et al. 1997 disruption of the calcium homeostasis morrison et al. 1996 ; roy et al. 1998 cytoskeletal abnormalities wong et al. 1995 fas ligand fasl mediated death raoul et al. 2002 and deregulation of cdk5 cyclin dependent kinase 5 nguyen et al. 2001a . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | rt of the spinal cord are microglial cells see fig 3 laflamme et al. 2001 kappab alpha [inhibitory protein of nuclear factor kappab nf kappab ] index of nf kappab activity tumor necrosis factor alpha tnf alpha and cd14 data not shown . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor alpha | 1.0 | n l5 segment and cervical part of the spinal cord are microglial cells see fig 3 laflamme et al. 2001 kappab alpha [inhibitory protein of nuclear factor kappab nf kappab ] index of nf kappab activity tumor necrosis factor alpha tnf alpha and cd14 data not shown . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the proapoptotic cytokine tnf alpha is likely to play a determinant role in this model. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the endotoxin lps is able to trigger transcriptional activation of the gene encoding tnf alpha in microglial cells across the cns and tnf alpha gene expression progressively increased in the spinal cord of sod1 mice nadeau and rivest 2000 alpha levels are also found in the csf of als patients poloni et al. 2000 kappab pathway which is critic |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the bright field b.f. and dark field photomicrographs depict representative examples of the hybridization signal for tnf alpha b il 12 c and tlr2 d mrna in the reticular formation just above the olivary complex. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the bright field b.f. and dark field photomicrographs depict representative examples of the hybridization signal for tnf alpha il 12 and tlr2 mrna in the l5 segment of the spinal cord a . |
| 18809 | TUBA1B | tubulin, alpha 1b | alpha tubulin | 1.0 | actin and alpha tubulin were used as controls for loadings. |
| 18809 | TUBA1B | tubulin, alpha 1b | alpha tubulin | 1.0 | membranes were incubated with antibodies against sod1 biodesign; santa cruz biotechnology santa cruz ca alpha tubulin b512; sigma and actin mab 1501; chemicon temecula ca . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we next assessed the transcriptional activation of the receptor of innate immunity tlr2 and the proapoptotic cytokine tnf alpha in the sod1 mice challenged chronically with lps. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | the robust expression of tlr2 mrna fig 3 d g is associated with strong hybridization signals for the genes encoding the proapoptotic cytokines tnf alpha andinterleukin 12 il 12 in degenerating efferent fiber tracts of the brain fig 3 b c and in degenerating ventral spinal horns fig 4 a rows 2 4 . |
| 5438 | IFNG | interferon, gamma | interferon gamma | 1.0 | to determine whether upregulated innate immunity transfers to the adaptive form we performed in situ hybridization on spinal cord and brain tissues using highly sensitive probes for interferon gamma ifn gamma and il 12 two cytokines essential for the transfer from the innate to the acquired immunity. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | isera dr. a. israel institut pasteur paris france for the mouse i kappab alpha cdna dr. d. radzioch mcgill university montr_amp_eacute;al qu_amp_eacute;bec canada for the plasmid containing the mouse tnf alpha cdna dr. i. campbell the scripps research institute la jolla ca for the mouse ifn gamma cdna dr. k. pahan university of nebraska lincoln ne for the mouse il 12p40 cdna and dr. li huei tsai for hostin |