Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In systemic autoimmune-prone (NZB x NZW)F1 (NZB/W F1) mice, B-cell abnormalities characterized by hypergammaglobulinaemia accompanying autoantibodies have been thought to be a main cause of the disease. To examine a possible regulatory role of B cells in the disease manifestations, we injected, intravenously (i.v.), normal or autoimmune B cells into non-irradiated NZB/W F1 mice. The injection of splenic B cells from major histocompatibility (MHC)-matched or allogeneic normal mice caused a marked decrease in serum immunoglobulin G (IgG) levels of autoantibodies, delayed the appearance of proteinuria and prolonged life span, whereas treatment with splenic B cells from NZB/W F1 or X-linked immunodeficient (Xid) mice failed to suppress the autoimmunity. Moreover, in vitro polyclonal antibody responses to lipopolysaccharide (LPS) of NZB/W F1-derived B cells from the treated mice were markedly reduced. Interestingly, the treatment of NZB/W F1 mice at 16, 18 and 20 or at 20, 22 and 24 weeks of age was more effective than that at 6, 8 and 10 weeks. The treatment also inhibited the development of surface IgG+ (sIgG+) B cells and splenomegaly, prominent in aged NZB/W F1 mice. In addition, when untreated NZB/W F1 responding B cells were precultured with normal B cells in vitro for 3 days, they also diminished the autoantibody production to subsequent LPS stimulation. Hence, the present results imply a novel function of normal B cells to ameliorate autoimmune disease in NZB/W F1 mice by correcting their B-cell abnormalities, and indicate that NZB/W F1 and Xid mice possess defects in this regulatory B-cell function.
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PMID:A novel function of B lymphocytes from normal mice to suppress autoimmunity in (NZB x NZW)F1 mice. 1080 65

Outer membrane proteins (OMPs) and rough lipopolysaccharide (R-LPS), the main surface antigens of Brucella ovis, display surface-exposed epitopes. Mixtures of monoclonal antibodies (mAbs) to both antigens were previously shown to protect mice against a B. ovis challenge. To further identify the antigens involved, seven mAbs against Brucella OMPs (Omp10, Omp16, Omp19, Omp25, Omp31, Omp2b and Omp1) and three to R-LPS were tested for protection either individually or in combinations. Significant reduction in spleen infection in challenged mice, relative to controls, was used as the protection criteri. Controls included nonimmunized mice and mice given an irrelevant, anti-O-polysaccharide (OPS), mAb. For comparison, a group received a mouse serum containing antibodies to both OMPs and R-LPS; this serum was prepared by immunization with a B. ovis hot-saline extract which, as described previously, induces protective immunity in mice and rams. Significant protection was observed with both mAbs to OMPs and R-LPS. mAbs to Omp16, Omp19 and Omp31 afforded the highest protection and prevented the development of splenomegaly. The protective effect of mAb to Omp31 was not interfered with by nonprotective mAbs in different mixtures. The data presented confirm the protective role of antibodies to OMPs and R-LPS against B. ovis, and identify several OMPs, especially Omp31, which are promising candidates for a subunit vaccine against ram epididymitis.
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PMID:Identification of protective outer membrane antigens of Brucella ovis by passive immunization of mice with monoclonal antibodies. 1086 93

C3H/HeJ mice have an impaired ability to respond to lipopolysaccharide (LPS) due to a mutation in the gene that encodes Toll-like receptor 4 (TLR4). The effect of TLR4 deficiency on host responses to endodontic infections is unknown. In the present study, we compared periapical bone destruction, sepsis, and inflammatory cytokine production in LPS-hyporesponsive C3H/HeJ and wild-type control C3H/HeOuJ mice. The mandibular first molars of both strains were subjected to pulpal exposure and infection with a mixture of four anaerobic pathogens, Prevotella intermedia, Fusobacterium nucleatum, Streptococcus intermedius, and Peptostreptococcus micros. At sacrifice on day 21, TLR4-deficient C3H/HeJ mice had significantly reduced periapical bone destruction compared to wild-type C3H/HeOuJ mice (P < 0.001). The decreased bone destruction in C3H/HeJ correlated with reduced expression of the bone resorptive cytokines interleukin 1alpha (IL-1alpha) (P < 0.01) and IL-1beta (P < 0.05) as well as the proinflammatory cytokine IL-12 (P < 0.05). No significant differences were seen in the levels of gamma interferon, tumor necrosis factor alpha (TNF-alpha), or IL-10 between the two strains. The expression of IL-1alpha, IL-1beta, TNF-alpha, IL-10, and IL-12 were all significantly reduced in vitro in macrophages from both TLR4-deficient C3H/HeJ and C57BL/10ScNCr strains, compared to wild-type controls. Notably, the responses of TLR4-deficient macrophages to both gram-positive and gram-negative bacteria were similarly reduced. Neither C3H/HeJ nor C3H/HeOuJ mice exhibited orofacial abscess development or infection dissemination as determined by splenomegaly or cachexia. We conclude that intact TLR function mediates increased proinflammatory responses and bone destruction in response to mixed anaerobic infections.
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PMID:Toll-like receptor 4-deficient mice have reduced bone destruction following mixed anaerobic infection. 1089 73

The aim of this study was to investigate whether increased hepatic oxidative stress could be visualised in living animals before the onset of obvious liver injury. Acute hepatic injury was induced in mice by priming with heat-killed Corynebacterium parvum followed by injection of a low dose of lipopolysaccharide (LPS). Low frequency band electron spin resonance-computed tomography (ESR-CT) with 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) was used to visualize hepatic oxidative stress. Biochemical and histological investigations performed 3 h after injection of LPS revealed no obvious injury to the liver. Conversely, significant hepatic oxidative stress could be detected at this time. Nitroxides such as carbamoyl-PROXYL are rapidly reduced to the corresponding hydroxylamine in vivo. resulting in the disappearance of their ESR signals. The kinetic clearance of carbamoyl-PROXYL after intravenous administration was delayed significantly in mice that had received LPS, due to impairment of the reduction system by hepatic oxidative stress. ESR-CT of the murine abdomen revealed a high intensity area of carbamoyl-PROXYL which consisted mainly of the liver and enlarged spleen. Time-course observations with ESR-CT using carbamoyl-PROXYL showed that the high intensity area in the liver disappeared rapidly due to reduction of carbamoyl-PROXYL. Three hours after LPS injection into the same mouse, ESR-CT images were obtained again by intravenous injection of carbamoyl-PROXYL. The ESR-CT images of the mouse with hepatic oxidative stress clearly showed that the high intensity area of carbamoyl-PROXYL in the liver persisted for a long period of time. This study is the first report to describe the use of in vivo ESR-CT for visualizing the state of increased oxidative stress in the liver before the onset of obvious hepatic injury.
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PMID:In vivo imaging of increased oxidative stress in the liver by electron spin resonance-computed tomography. 1148 75

Endotoxin has been identified as a principal mediator of sepsis, often with resulting multiple organ failure. Although interferon gamma (IFN-gamma) has a central role in controlling bacterial infection through the activation of macrophages and T lymphocytes, it can also enhance the harmful effects of the inflammatory response. To examine the role of IFN-gamma in lipopolysaccharide (LPS)-induced injury, we administered LPS (20 or 800 microg/mouse) alone or as low-dose LPS (20 microg/mouse) 7 days after heat-killed Propionibacterium acnes (P. acnes) injection into wild-type C57BL/6 (B6) mice or IFN-gamma-deficient (GKO) mice (B6 background). Although low-dose (20 microg) LPS alone had no effect on survival, the administration of 800 microg LPS alone resulted in 100% mortality in both B6 and GKO mice without significant hepatic mononuclear cellular infiltration or differences in elevated plasma tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-12 levels. In contrast, mortality after low-dose (20 microg) LPS challenge in P. acnes-primed B6 mice was 100%, but 0% in GKO mice. In vivo plasma cytokine (IFN-gamma, TNF-alpha, IL-6, and IL-12) levels and in vitro cytokine production by hepatic mononuclear cells were significantly higher in B6 mice compared with GKO mice. Associated hepatic mononuclear cellular infiltration, multifocal liver necrosis, hepatomegaly, and splenomegaly were found in B6 mice, but not in GKO mice. Finally, the anti-inflammatory NK1.1+CD4+ cell proportion of hepatic infiltrating mononuclear cell numbers 7 days after P. acnes administration was significantly reduced in B6 compared with GKO mice, whereas the proportion of inflammatory NK1.1+CD4- cells was increased. In conclusion, these data suggest that IFN-gamma mediates P. acnes-primed low-dose LPS injury through the hepatic infiltration of mononuclear cells and the subsequent elevation of inflammatory cytokines after LPS challenge, whereas the lethal effects of high-dose LPS alone does not depend on the presence of IFN-gamma.
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PMID:The resistance of P. acnes--primed interferon gamma-deficient mice to low-dose lipopolysaccharide-induced acute liver injury. 1191 26

Stimulation of splenocytes from socially stressed mice [social disruption (SDR)] with Gram-negative bacterial lipopolysaccharide (LPS) revealed a state of functional glucocorticoid (GC) resistance. LPS-stimulated splenocytes were less sensitive to the inhibitory effects of corticosterone. This study demonstrated that activation signals were required for the expression of splenic GC resistance. The results demonstrated that six cycles of SDR induced splenomegaly and increased the number of CD11b-positive monocytes. SDR also increased the viability of cultured, nonstimulated splenocytes, and addition of corticosterone reduced the viability of these cells in a dose-dependent manner. However, following stimulation with LPS, the sensitivity of SDR splenocytes to GC was reduced. Similar results were obtained using lipid A, a fraction of the LPS molecule that binds to Toll-like receptor (TLR)4. Furthermore, C3H/HeJ mice that do not possess a functional TLR4 molecule responded to SDR with an increased number of CD11b-positive monocytes in the spleen and increased viability of nonstimulated splenocytes. However, neither LPS nor lipid A stimulation resulted in the expression of GC resistance. Together, these findings suggest that the expression of GC resistance in response to SDR requires a second signal that can be provided by ligation of TLR4.
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PMID:Expression of glucocorticoid resistance following social stress requires a second signal. 1296 Feb 58

The immunomodulatory effects of Mycoplasma fermentans-derived membrane lipoprotein (LAMPf) in BALB/c mice were examined. When injected intraperitoneally into mice, LAMPf induced a transitory splenomegaly followed by a suppression of the spleen cell proliferation in response to concanavalin A, whereas responses to lipopolysaccharide and to LAMPf were unchanged. The intravenous injection of a large dose of LAMPf induced leukopenia and granulocyte-macrophage colony-stimulating factor (GM-CSF) activity in serum. A synthetic analogue of its N-terminal lipopeptide with ability to activate macrophages (MALP-2) was also able to induce GM-CSF in serum. Interestingly, GM-CSF induction by a low dose of MALP-2 was not associated with significant leukopenia. These data revealed that the in vitro moduline properties of mycoplasmal lipoproteins and lipopeptides correlate with interesting in vivo immunomodulatory effects.
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PMID:In vivo immunomodulation by Mycoplasma fermentans membrane lipoprotein. 1505 72

Social disruption (SDR) is an effective model of social stress associated with an enhanced inflammatory reactivity of the immune system. The aim of the present study was to further describe SDR effects on cytokine production by spleen cells, testing selectively monocyte and T cell functions as a result of this stressor. For this purpose, splenocytes from control mice (C) and mice socially stressed for 7 days (SDR) were cultured in the presence of lipopolysaccharide (LPS) or concanavalin A (Con A). Splenocyte proliferation, cytokine production and sensitivity of spleen cells to corticosterone were assessed in vitro. The humoral response to keyhole limpet hemocyanin (KLH) immunization was assessed. SDR induced splenomegaly and enhanced splenocyte basal proliferation. The pro-inflammatory influence of SDR was confirmed by an increased release of interleukin-6 (IL-6) by LPS-stimulated cultures and by a reduced sensitivity of spleen cells to the anti-inflammatory effect of corticosterone. The mechanism increasing cytokine production in response to LPS was cytokine specific, since among inflammatory cytokines, IL-6 but not interferon-gamma (IFN-gamma) was enhanced by stress. In stressed mice, the increase in IL-6 and IFN-gamma and the decrease in IL-10 release in Con A-stimulated cultures indicate that SDR did not modify the Th1/Th2 cytokine balance but globally activated T cells. Plasma anti-KLH antibody levels were similar in both groups. Wounded and non-wounded mice presented similar responses to stress. This study shows that social disruption stress enhances the reactivity of cells from both the acquired and innate immune systems.
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PMID:Cytokine production by spleen cells after social defeat in mice: activation of T cells and reduced inhibition by glucocorticoids. 1520 33

Induction of heme oxygenase-1 (HO-1) is protective in tissue injury in models of allograft rejection and vascular inflammation through either prevention of oxidative damage or via immunomodulatory effects. To examine the specific role of HO-1 in modulating the immune response, we examined the differences in immune phenotype between HO-1 knockout (HO-1(-/-)) and wild-type (HO-1(+/+)) mice. Consistent with previous findings, marked splenomegaly and fibrosis were observed in HO-1(-/-) mice. The lymph nodes of HO-1-deficient mice demonstrated a relative paucity of CD3- and B220-positive cells, but no such abnormalities were observed in the thymus. Flow cytometric analysis of isolated splenocytes demonstrated no differences in the proportions of T lymphocytes, B lymphocytes or monocytes/macrophages between the HO-1(-/-) and HO-1(+/+) mice. Significantly higher baseline serum IgM levels were observed in HO-1(-/-) versus HO-1(+/+) mice. Under mitogen stimulation with either lipopolysaccharide or anti-CD3/anti-CD28, HO-1(-/-) splenocytes secreted disproportionately higher levels of pro-inflammatory Th1 cytokines as compared to those from HO-1(+/+) mice. These findings demonstrate significant differences in the immune phenotype between the HO-1(-/-) and the HO-1(+/+) mice. The absence of HO-1 correlates with a Th1-weighted shift in cytokine responses suggesting a general pro-inflammatory tendency associated with HO-1 deficiency.
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PMID:Heme oxygenase-1 modulates early inflammatory responses: evidence from the heme oxygenase-1-deficient mouse. 1533 27

We previously demonstrated that delivery of CpG oligodeoxynucleotide (ODN) to vaginal mucosa induced an innate mucosal antiviral state that protected against intravaginal challenge with herpes simplex virus (HSV)-2. We report that mucosal, but not systemic, delivery of ligands for Toll-like receptor (TLR)-3, but not TLR4, induced protection against genital HSV-2 challenge that was not accompanied by the local inflammation and splenomegaly seen after treatment with CpG ODN. Surprisingly, TLR4 messenger (m) RNA expression was shown to be higher than that of TLR3 or TLR9 in murine genital mucosa. Similarly, murine RAW264.7 cells were shown to express more mRNA for TLR4 than TLR3 or TLR9, yet treatment of these cells with double-stranded RNA provided greater protection than lipopolysaccharide or CpG ODN. These results indicate that TLR3 ligand induces a more potent antiviral response than TLR4 and TLR9 ligands and may be a safer means of protecting against sexually transmitted viral infections.
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PMID:Toll-like receptor (TLR)-3, but not TLR4, agonist protects against genital herpes infection in the absence of inflammation seen with CpG DNA. 1549 42


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