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)

Activation of peritoneal B-1 cells triggers autoimmune anemia in anti-erythrocyte Ig transgenic mice (HL mice). Numbers of peritoneal B-1 cells and Ig-producing cells were negligible in the T cell-deficient HL mice generated by the cross with RAG-2-/- mice (RAG-2-/- x HL mice). Proliferation and activation of B-1 cells in RAG-2-/- x HL mice were recovered by fetal thymus transfer, indicating involvement of T cells in B-1 cell-mediated autoimmune hemolytic anemia. Involvement of T cells in proliferation and activation of B-1 cells could be by-passed by administration of lipopolysaccharide (LPS), IL-5 or IL-10 to RAG-2-/- x HL mice. Administration of LPS elevated the serum IL-10 level in HL, RAG-2-/- x HL and normal mice. Proliferation and activation of B-1 cells were blocked by an anti-IL-10 antibody in conventionally bred as well as LPS-treated HL mice. Taken together, IL-10 plays a pivotal role in activation of peritoneal B-1 cells.
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PMID:Involvement of IL-10 in induction of autoimmune hemolytic anemia in anti-erythrocyte Ig transgenic mice. 972 89

We have investigated the influence of age on B-cell responsiveness. The present study showed that the B-cell mitogen, lipopolysaccharide (LPS), similarly stimulated the proliferation of purified B lymphocytes obtained from either young mice (3 months) or old mice (24 months). In contrast, expression of the differentiation marker, alkaline phosphatase (ALP), was about fourfold higher in young mice than in older mice upon stimulation with LPS or with dextran sulfate (DXS) and interleukin-5 (IL-5). The occurrence of apoptosis during aging was then studied: unexpectedly, spontaneous cell death was double in B lymphocytes from young mice compared to older animals. Stimulation with DXS with or without IL-5 rescued B lymphocytes from cell death in young mice but protection decreased with aging, and no longer occurred in 24-month-old mice B cells. Meanwhile, the protective activity conferred by IL-4 was maintained at similar levels throughout aging. However, B cells from old mice were more responsive to apoptosis induction with cycloheximide, dibutyryl cAMP and dexamethasone. Together, the present results indicate an age-associated alteration in apoptosis and activation of B lymphocytes which could contribute to the age-related decline of the immune response.
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PMID:Age-associated modulation of apoptosis and activation in murine B lymphocytes. 972 4

Interleukin (IL)-18 induces interferon (IFN)-gamma synthesis and synergizes with IL-12 in T helper type 1 (Th1) but not Th2 cell development. We report here that IL-18 receptor (IL-18R) is selectively expressed on murine Th1 but not Th2 cells. IL-18R mRNA was expressed constitutively and consistently in long-term cultured clones, as well as on newly polarized Th1 but not Th2 cells. IL-18 sustained the expression of IL-12Rbeta2 mRNA, indicating that IL-18R transmits signals that maintain Th1 development through the IL-12R complex. In turn, IL-12 upregulated IL-18R mRNA. Antibody against an IL-18R-derived peptide bound Th1 but not Th2 clones. It also labeled polarized Th1 but not Th2 cells derived from naive ovalbumin-T cell antigen receptor-alphabeta transgenic mice (D011.10). Anti-IL-18R antibody inhibited IL-18- induced IFN-gamma production by Th1 clones in vitro. In vivo, anti-IL-18R antibody reduced local inflammation and lipopolysaccharide-induced mortality in mice. This was accompanied by shifting the balance from Th1 to Th2 responses, manifest as decreased IFN-gamma and proinflammatory cytokine production and increased IL-4 and IL-5 synthesis. Therefore, these data provide a direct mechanism for the selective effect of IL-18 on Th1 but not Th2 cells. They also show that the synergistic effect of IL-12 and IL-18 on Th1 development may be due to the reciprocal upregulation of their receptors. Furthermore, IL-18R is a cell surface marker distinguishing Th1 from Th2 cells and may be a therapeutic target.
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PMID:Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells. 978 25

Mice with a null mutation of the betac chain of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors (betac-null mice) develop an alveolar proteinosis-like lung disease. The pathogenesis of this disease is uncertain and, although a defect in alveolar macrophage function has been postulated, no previous analysis of mature hematopoietic cells in mice with alveolar proteinosis has been reported. Therefore, we undertook a functional analysis of the mature hematopoietic cell compartment in betac-null mice. In addition, we reexamined the roles of the GM-CSF receptor chain and the betac chain in signaling by GM-CSF. Neutrophils and macrophages from betac-null mice were capable of normal survival and phagocytosis in the absence of stimulus and of similar levels of nitric oxide production in response to interferon-gamma and lipopolysaccharide. GM-CSF-mediated augmentation of survival, phagocytosis, and hydrogen-ion production were absent in neutrophils from betac-null mice. Interestingly, we were unable to show any ability of the GM-CSF receptor -chain alone to mediate glucose transport in these cells. In keeping with the betac-null mice lung pathology, examination of lavage fluid from the lungs of betac-null mice showed increased cellularity. This was caused by an increase in the number of lymphocytes, neutrophils, and macrophages. Large foamy cells in the lavage fluid from betac-null mice were identified as macrophages using immunohistochemistry. Functional analysis showed that these betac-null alveolar macrophages were capable of phagocytosis but uptake of colloidal carbon and cellular adhesion were reduced. In summary, mature hematopoietic cells with a null mutation of the betac receptor were unable to perform GM-CSF-mediated hematopoietic cell functions including glucose transport, but responded normally to a range of other ligands.
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PMID:Functional analysis of mature hematopoietic cells from mice lacking the betac chain of the granulocyte-macrophage colony-stimulating factor receptor. 983 17

The spin-trapping compound phenyl N-tert-butylnitrone (PBN) affords protection from the lethality of septic shock in rodents. Previous studies have shown that PBN elicits its protection by inhibiting inducible nitric oxide synthase (iNOS) induction. In the present study, using the lipopolysaccharide (LPS) rat septic shock model, we determined the expression of various cytokine genes (tumor necrosis factor (TNF)-alpha, TNF-beta, interferon (IFN)-gamma, interleukin (IL)-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, and IL-10) and the activation of transcription factors nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1) in the liver tissue, 30 min and 3 h after LPS administration. The effects of PBN preadministration on the production levels were also investigated. The results show that LPS (4 mg/kg, ip) induced the production of the cytokine genes and increased the nuclear protein level of NF-kappaB within 30 min after LPS administration. Preadministration of PBN (150 mg/kg, ip) significantly down-regulated the production of cytokine genes (TNF-alpha by 94%, IL-1 by 63%, and IL-1 by 70%) and reduced the nuclear protein level of NF-kappaB by 75% and AP-1 by 72% at 3 h after LPS injection. These results demonstrate that PBN, in addition to its iNOS induction inhibition, also has multiple anti-inflammatory effects in septic shock, via modulation of the production of the key inflammatory mediators.
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PMID:Expression of cytokines and activation of transcription factors in lipopolysaccharide-administered rats and their inhibition by phenyl N-tert-butylnitrone (PBN). 1006 57

To investigate the early events of Helicobacter pylori infection in a mouse model, CD1 mice were infected with a type I (CagA+/VacA+) H. pylori strain. Up to 4 weeks after infection the majority of gastric tissue biopsies were positive in culture. Immunohistochemical analysis showed that inflammatory changes started to occur after 3 weeks. Four weeks after infection a significant increase in T cells was observed in the cardia/corpus region of the stomachs of infected mice. These T cells were CD4+ and CD8+, and they were located in an area with increased expression of MHC class II antigens. In 50% of the infected mice also an increased number of mast cells was seen. Furthermore, aggregates of B and T cells were present in the submucosa. Characterization of cytokines by immunohistochemistry showed an increase in IL-5-secreting cells in the inflamed area of the infected stomach. No difference was observed between interferon-gamma (IFN-gamma)-, IL-4- and IL-10-secreting cells in control and infected mice. These results suggest that no polarized T-helper cell response was present at this early phase of infection. Infection with H. pylori also induced a serum response and especially IgG was increased after 4 weeks of infection. However, no particular increase in IgG1, IgG2a or IgG3 isotype was observed. Part of the serum antibodies was directed against lipopolysaccharide (LPS), but no evidence for anti-Lewis antibodies or antibodies against epitopes on the gastric mucosa was found.
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PMID:The inflammatory response in CD1 mice shortly after infection with a CagA+/VacA+ Helicobacter pylori strain. 1019 13

IL-5, IL-10 and lipopolysaccharide (LPS) are known to activate B-1 cells in vivo in normal mice and anti-red blood cell autoantibody transgenic mice (HL mice). To assess the exact role of IL-5 in proliferation and activation of peritoneal B-1 cells, we analyzed IL-5 receptor alpha chain-deficient HL (IL-5Ralpha-/- x HL) mice generated by the cross between IL-5Ralpha-/- and HL mice. In IL-5Ralpha-/- x HL mice, Ig-producing B-1 cells in the peritoneal cavity were negligible, although the total number of B-1 cells in the peritoneal cavity were as many as 30% of that in HL mice. Moreover, LPS- or IL-10-induced differentiation of B-1 cells into antibody-producing cells was severely impaired in IL-5Ralpha-/- x HL mice. We also used in vivo 5-bromo-2'-deoxyuridine labeling to estimate the proliferation of B-1 cells in IL-5Ralpha-/- mice. The absence of IL-5Ralpha did not affect spontaneous proliferation of peritoneal B-1 cells. However, induced proliferation of peritoreal B-1 cells by oral administration of LPS was markedly impaired in IL-5Ralpha-/- mice. These results suggest that IL-5 is required for activation-associated proliferation of B-1 cells but not for their spontaneous proliferation and support the idea that IL-5 plays an important role on the induction of autoantibody production from B-1 cells.
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PMID:Requirement of IL-5 for induction of autoimmune hemolytic anemia in anti-red blood cell autoantibody transgenic mice. 1036 Sep 74

Mice deficient in various mismatch repair (MMR) enzymes were examined to determine whether this repair pathway is involved in antibody class switch recombination. Splenic B cells from mice deficient in Msh2, Mlh1, Pms2, or Mlh1 and Pms2 were stimulated in culture with lipopolysaccharide (LPS) to induce immunoglobulin (Ig)G2b and IgG3, LPS and interleukin (IL)-4 to induce IgG1, or LPS, anti-delta-dextran, IL-4, IL-5, and transforming growth factor (TGF)-beta1 to induce IgA. After 4 d in culture, cells were surface stained for IgM and non-IgM isotypes and analyzed by FACS((R)). B cells from MMR-deficient mice show a 35-75% reduction in isotype switching, depending on the isotype and on the particular MMR enzyme missing. IgG2b is the most affected, reduced by 75% in Mlh1-deficient animals. The switching defect is not due to a lack of maturation of the B cells, as purified IgM(+)IgD(+) B cells show the same reduction. MMR deficiency had no effect on cell proliferation, viability, or apoptosis, as detected by [(3)H]thymidine incorporation and by propidium iodide staining. The reduction in isotype switching was demonstrated to be at the level of DNA recombination by digestion-circularization polymerase chain reaction (DC-PCR). A model of the potential role for MMR enzymes in class switch recombination is presented.
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PMID:Reduced isotype switching in splenic B cells from mice deficient in mismatch repair enzymes. 1043 Jun 19

The intention of this study was to mimic a naturally occurring stimulation by allergens and bacterial infection in order to determine whether specific allergen-induced, inflammatory responses may be changed or modified by bacterial products. Blood leukocytes from six atopic and six nonatopic individuals were examined for their surface expression of CD154, CD11a, and HLA-DR molecules and for secretion of IgE, eosinophil cationic protein (ECP), and the cytokines interleukin (IL)-4 and IL-5. Signals through CD154 are required for activation and proliferation of effector cells associated with the allergic, inflammatory response. HLA-DR and CD11a/CD18-mediated interactions are also involved in T- and B-cell functions. Birch-pollen (BP) allergens induced CD154 expression on CD3-positive lymphocytes only in atopic individuals. In nonatopics, the expression of CD154 could be induced only after exposure to BP and subsequent lipopolysaccharide (LPS) stimulation. Levels of CD154 expression were always higher in atopics than nonatopics. CD11a and HLA-DR expressions were upregulated, irrespective of atopic state, after BP and/or LPS stimulation. The increased secretion of IL-5 and total IgE in BP-supplemented cell cultures indicated that an allergic response had occurred. In conclusion, the results of this report do not support the hypothesis of a changed inflammatory response stimulated by the combined action of bacteria and allergens, as compared to allergen provocation alone.
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PMID:Allergen-stimulated expression of CD154 (CD40 ligand) on CD3+ lymphocytes in atopic, but not in nonatopic individuals. Modulation by bacterial lipopolysaccharide. 1044 28

Corticosteroids (CS) are potent immunosuppressive agents that are known to affect T cell-mediated inflammation by the inhibition of proliferation and cytokine production, as well as the immunostimulatory function of monocytes and macrophages. Not much is known of the effect of corticosteroids on dendritic cells (DC), the professional T cell stimulatory antigen-presenting cells. We report that the endogenous CS hydrocortisone and the synthetic CS clobetasol-17-propionate strongly inhibited the production of the inflammatory mediators interleukin (IL)-12 p70, tumor necrosis factor alpha (TNF-alpha), and IL-6 by lipopolysaccharide (LPS)-stimulated monocyte-derived immature DC (iDC) in vitro. In contrast, the stimulatory capacity, antigen uptake, and the expression of costimulatory molecules were not affected. In accordance with the decreased production of IL-12 p70, CS-treated iDC induced less production of the inflammatory Th1 cytokine interferon-y and enhanced levels of the Th2 cytokines IL-10 and IL-5 in staphylococcal enterotoxin B-stimulated CD4+ Th cells. Furthermore, CS inhibited the maturation of iDC as assessed by the lack of expression of CD83 as well as by the prevention of the loss of antigen uptake capacities. These type 3 DC (DC3) matured in the presence of CS produce less IL-12 p70 and have a decreased T cell stimulatory capacity. Moreover, uncommitted T cells that encounter the CS-induced DC3 develop into Th2-biased cells, which may additionally decrease the Th1-mediated tissue damage but, on the other hand, Th2 cytokines may promote undesirable elevation of IgE and eosinophilia. These findings indicate that suppression of T cell-mediated inflammation by CS not only relies on direct effects on T cells, but also on various effects on DC, their professional antigen-presenting cells.
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PMID:Corticosteroids inhibit the production of inflammatory mediators in immature monocyte-derived DC and induce the development of tolerogenic DC3. 1044 54


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