Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fumaric acid derivates have been shown to stimulate T helper-2-cytokines (interleukin (IL)-4, -5) without affecting the T-helper-1-cytokine (IL-2, interferon (IFN)-gamma)-response. Herein, the influence of systemic treatment with the fumaric acid derivate dimethylfumarate (DMF) on the secretion of T helper-cytokines and the development of HSV-1 stromal keratitis (HSK) was studied in mice. The corneas from BALB/c mice were infected with 10(5) PFU of HSV-1 (KOS strain). While one group of mice was treated intraperitoneally with PBS, another group of mice received DMF at 15 mg/kg of body weight. Expression of IL-2, -4, -10 and IFN-gamma was analysed in HSV-1 activated lymphocytes by ELISA. The severity of epithelial and stromal herpetic keratitis was investigated clinically. Corneas were studied for the inflammatory cell infiltration, and the CD3-, CD4- and CD8-positive cells were analysed by immunohistochemistry. The IL-2, -4, 10 and IFN-gamma content was measured in the corneas. Virus replication in the eyes was analysed by a plaque-assay. The DTH-response, the HSV-specific T cell proliferation and the serum neutralizing antibody-titres were investigated. DMF increased IL-4 and IL-10, but not IL-2 and IFN-gamma, secretion in activated lymphocytes from the spleen. Incidence and severity of stromal HSV-1 keratitis was reduced in the DMF group (P < 0.01). In the corneas from DMF-treated mice, the numbers of CD3+ and CD4+ cells were decreased and IL-4 was increased. Severity of epithelial disease and the virus-clearance from the eyes did not differ between the PBS and DMF group of mice. DTH, HSV-specific T cell proliferation and the neutralizing antibody-titres were not impaired. DMF increased the T helper-2-cytokine secretion in activated lymphocytes. After corneal HSV-1 infection, corneas from DMF treated mice had increased IL-4 content. This is associated with an improvement of herpetic stromal keratitis and reduced corneal T cell infiltration. DMF did not impair the systemic antiviral response.
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PMID:Improvement of herpetic stromal keratitis with fumaric acid derivate is associated with systemic induction of T helper 2 cytokines. 1617 74

We performed an asthma mice model in this study and aimed to investigate the levels of mediators in bronchoalveolar lavage fluid (BALF), and lung tissue, and the pathological changes response to the steroid treatment. BALB/c mice divided into three groups. PBS was applied to group 1 (control group). Asthma model was performed by exposing to ovalbumin in group 2 and 3. DEX was injected to group 3. After the last DEX dose all of the mice were killed by cervical dislocation. The samples of BALF and lung tissue were obtained. IL-4 and IL-5 levels of all samples were measured and inflammatory cells were counted in BALF. Evident eosinophilia was determined in BALF of group 2. Eosinophil numbers were lower in group 3 when compared with group 2 and this was statistically significant (p< 0.001). Inflammatory cell infiltration, eodema and hyperemia observed around the walls of bronchus and bronchiols in group 2. The lungs of group 3 had normal histological appearance. Both two cytokin levels of lung tissue were higher in group 2 than group 1, and this was statistically significant (for IL-4 p< 0.003, and for IL-5 p< 0.002). In group 3, both two cytokin levels were statistically lower than group 2 (for IL-4 p< 0.001, and for IL-5 p< 0.026). In BALF samples both two cytokin levels were higher in group 2 than group 1, and this was statistically significant (for IL-4 p< 0.004, and for IL-5 p< 0.001). In group 3, both two cytokin levels were lower than group 2, but it was not statistically significant (p> 0.05). In conclusion, it is thought that antiinflammatory effect of glucocorticoids occur by inhibiting the formation of IL-4, IL-5 and eosinophils.
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PMID:[Investigating the anti-inflammatory effect of dexamethasone in an asthma mouse model]. 1625 83

The fruit juice of black currant was found to contain a polysaccharide-rich substance, which was designated cassis polysaccharide (CAPS), with macrophage-stimulating activity. Especially, its interleukin (IL)-1beta-inducing activity was remarkably high, compared with other fruit juice preparations. CAPS was found to consist of rhamnose, mannose, arabinose, galactose, xylose, and glucose in a molar ratio of 11.3:0.9:54.1:29.8:2.0:1.9. CAPS turned out to be partitioned into a soluble component (CAPS-l.m.) and a precipitable component (CAPS-h.m.) with mean MWs of 80,000 and 600,000 respectively in 45% (v/v) ethanol solution. At least in vitro, CAPS-l.m. rather than CAPS-h.m. appeared to play an important role in macrophage activation. Oral administration of black currant juice and CAPS to Ehrlich carcinoma-bearing mice retarded the growth of the solid tumor by 45% and 51% respectively. CAPS administration had a stimulatory effect on the release of IL-2, IL-10, interferon-gamma, and IL-4 from splenocytes in comparison with PBS treatment in tumor-bearing mice. The IL-4 level was, however, still lower than that exhibited by a group of normal mice. CAPS showed a certain cytotoxicity directly against tumor cells.
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PMID:Immunostimulatory effects of a polysaccharide-rich substance with antitumor activity isolated from black currant (Ribes nigrum L.). 1630 83

Mammalian pregnancy is a complex phenomenon allowing the maternal immune system to support its allogeneic fetus. Physiological pathways protecting the fetus from rejection are thought to be comparable with those leading to allograft acceptance. Heme oxygenase (HO)-1 is known to protect locally against rejection in transplantation models due to its anti-oxidant, anti-inflammatory and cytoprotective functions. Based on previous data on low HO-1 levels in placenta from mice undergoing abortion, we hypothesized that an up-regulation of HO-1 during pregnancy would avoid fetal rejection in the murine abortion combination CBA/J x DBA/2J, using BALB/c-mated CBA/J as normal controls. We injected pregnant mice undergoing abortion with 1 x 10(5) PFU of an adenoviral vector containing HO-1 and GFP (AdHO-1/GFP), and compared the pregnancy outcome with PBS- or 1 x 10(5) AdEGFP-treated abortion-prone mice and with PBS-treated normal pregnant mice. The abortion rate diminished significantly after adenoviral gene transfer of AdHO-1/GFP. The systemic and local IL-4/IFN-gamma ratio was augmented in AdHO-1-treated mice compared to abortion-prone mice. Interestingly, the HO-1 treatment up-regulated the ratio IL-10/TNF-alpha in spleen but not in decidual lymphocytes. HO-1-treated mice further showed diminished apoptosis rate and increased Bag-1 mRNA levels at the materno-fetal interface. Thus, we propose HO-1 as a key regulator of pregnancy success. HO-1 would exert its action by locally up-regulating the Th2/Th1 cytokine ratio and by further protecting tissues from apoptosis.
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PMID:Over-expression of heme oxygenase-1 by adenoviral gene transfer improves pregnancy outcome in a murine model of abortion. 1638 10

To gain insight into aberrant cytokine regulation in cystic fibrosis (CF), we compared the phenotypic manifestations of allergen challenge in gut-corrected CFTR-deficient mice with background-matched C57Bl6 (B6) mice. Aspergillus fumigatus (Af) antigen was used to mimic allergic bronchopulmonary aspergillosis, a peculiar hyper-IgE syndrome with a high prevalence in CF patients. CFTR-/-, C57BL/6 and FVB/NJ mice were sensitized with Af antigen by serial intraperitoneal injections. Control mice were mock sensitized with PBS. Challenges were performed by inhalation of Af antigen aerosol. After Af antigen challenge, histologic analysis showed goblet cell hyperplasia and lymphocytic infiltration in both strains. However, total serum IgE levels were markedly elevated in CF mice. Sensitized CF mice showed a five-fold greater IgE response to sensitization as compared with B6- and FVB-sensitized controls. Additional littermate controls to fully normalize for B6-FVB admixture in the strain background confirmed the role of CFTR mutation in the hyper-IgE syndrome. Cytokine mRNA levels of IL-5 and GM-CSF in the bronchoalveolar lavage (BAL) fluid, and BAL cell differentials indicated that CFTR mutation caused a shift from an IL-5-predominant to an IL-4-predominant cytokine profile. This system models a very specific type of airway inflammation in CF and could provide insights into pathogenesis and treatment of the disease.
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PMID:Enhanced IgE allergic response to Aspergillus fumigatus in CFTR-/- mice. 1642 81

Sheep were immunized by weekly oral infections with Haemonchus contortus for 9 weeks followed by anthelmintic treatment. They were challenged either 9 or 22 weeks later with PBS (sham controls) or one million exsheathed L3 surgically injected in the abomasum, and killed 24 h or 48 h later. Sheep challenged 9 weeks after immunization displayed varying degrees of tissue eosinophilia that showed a significant inverse relationship with the number of intra-epithelial mast cells (globule leucocytes). Close association of eosinophils with tissue larvae was observed mainly in the gastric pits (24 h) or on the mucosal surface (48 h). All L3-challenged sheep in this group had detectable globule leucocytes and tissue IL-4 mRNA, as measured by Southern blot RT-PCR. In contrast, sheep challenged 22 weeks after immunization had no detectable globule leucocytes or IL-4 mRNA and although they exhibited consistent tissue eosinophilia, eosinophils were not closely associated with tissue larvae. Scanning and transmission electron microscopy of sheep sensitized and rested for 9 weeks before challenge showed that L3 surrounded by eosinophils were at varying stages of damage and structural collapse. These studies strongly indicate that eosinophils can damage and probably kill gastrointestinal nematode larvae in vivo. In addition, they also suggest that effective killing by tissue eosinophils may depend on other microenvironmental factors such as intra-epithelial mast cells and IL-4.
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PMID:Eosinophil interactions with Haemonchus contortus larvae in the ovine gastrointestinal tract. 1644 9

Plasmid pBMC2 encoding antigen Bm86 from a Colombian strain of cattle tick Boophilus microplus, was used for DNA-mediated immunization of BALB/c mice, employing doses of 10 and 50microg, delivered by intradermic and intramuscular routes. Anti-Bm86 antibody levels were significantly higher compared to control mice treated with PBS. In the evaluation of immunoglobulin isotypes, significant levels of IgG2a and IgG2b were observed in mice immunized with 50microg of pBMC2. Measurement of interleukine (IL) levels (IL-4, IL-5, IL-12(p40)) and interferon-gamma (IFN-gamma) in the sera of mice immunized with pBMC2 indicated high levels of IL-4 and IL-5, although there were also significant levels of IFN-gamma. Mice immunized with pBMC2 showed antigen-specific stimulation of splenocytes according to the incorporation of bromodeoxyuridine and IFN-gamma secretion. In all trials, mice injected intramuscularly with 50microg of pBMC2 presented the highest immune response. Moreover, cattle immunized with this DNA vaccine showed antibody production significantly different to the negative control. In conclusion, these results suggest the potential of DNA immunization with pBMC2 to induce humoral and cellular immune responses against B. microplus.
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PMID:Immune response in mice and cattle after immunization with a Boophilus microplus DNA vaccine containing bm86 gene. 1705 51

Immunotherapy using T-cell epitope peptides or CpG DNA conjugated with allergenic protein is useful, although the mechanisms of these therapies differ. However, the combination of CpG DNA and peptide, but not protein, had not been documented. Therefore, we investigated CpG DNA conjugated with peptide to obtain positive synergistic effects. In the first experiment, mice were vaccinated with a conjugate of CpG DNA and Cry j 2 T-cell epitope peptide p246-259 (CpG-peptide); a mixture of CpG DNA and peptide (CpG+peptide); peptide alone, or PBS alone, and immunized with Cry j 2. In the second experiment, mice were immunized with Cry j 2 and injected with CpG-peptide, CpG+peptide, peptide only, or PBS only. In both experiments, Cry j 2-specific IgE, IL-4, and IL-5 were significantly lower in mice given CpG-peptide, versus those given CpG+peptide, peptide alone, or PBS alone. However, IgG2a, IgG2b and IFN-gamma did not increase in mice injected with CpG-peptide. In the third experiment, CpG-peptide significantly attenuated nasal symptoms (sneezing and nasal rubbing) compared to CpG+peptide, peptide alone, or PBS alone. Mice were also injected with a conjugate of CpG DNA and Cry j 2 protein (CpG-Cry j 2) or CpG-peptide to compare prime responses. Mice vaccinated with CpG-Cry j 2 generated Cry j 2-specific IgG1, whereas those vaccinated with CpG-peptide did not produce IgG1. This study demonstrated, for the first time, that immunotherapy with CpG DNA conjugated with a T-cell peptide is useful in preventing and treating allergic conditions.
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PMID:Immunotherapy with CpG DNA conjugated with T-cell epitope peptide of an allergenic Cry j 2 protein is useful for control of allergic conditions in mice. 1716 16

While evaluating vaccine efficacy against clinical Bordetella pertussis isolates in mice, after challenge vaccinated mice showed increased lung pathology with eosinophilia, compared to challenged, non-vaccinated animals. This led us to study bacterial clearance, lung pathology, lung TNF-alpha expression, and parameters of immediate hypersensitivity (IH), being serum IgE levels, eosinophil numbers in the bronchoalveolar lavage fluid, and ex vivo IL-4, IL-5, IL-10, IL-13, and IFN-gamma production by the bronchial lymph node cells. BALB/c mice received a combined Diphtheria (D), Tetanus (T), Poliomyelitis, and whole-cell Pertussis vaccine (WCV), a combined D, T, and three-component acellular Pertussis vaccine (ACV), aluminium hydroxide adjuvant, or PBS, 28 and 14 days before B. pertussis infection. Similarly treated non-infected mice were taken as a control. Infection induced pathology; this induction was stronger after (especially WCV) vaccination. WCV but not ACV vaccination induced TNF-alpha expression after challenge. After challenge, IH parameters were strongly increased by (especially ACV) vaccination. Vaccinated IL-4 KO mice showed similar clearance and pathology, in the absence of IgE and with reduced numbers of eosinophils. Vaccinated (Th1-deficient) T-bet KO mice showed reduced clearance and similar pathology. In summary, after challenge vaccination increased lung pathology, TNF-alpha expression (only WCV), and IH parameters. Th1 cells were critical for clearance.
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PMID:Lung pathology and immediate hypersensitivity in a mouse model after vaccination with pertussis vaccines and challenge with Bordetella pertussis. 1722 16

Although thorough studies on the immune reponse to rubella have been performed, less attention has been given to the cellular mechanism and mediators that shape the process. Specifically, information concerning the nature ofcytokine patterns involved in the immune response to Rubella vaccination is not avaliable. This study deals with cytokine production patterns of spleen cells from Balb/c mice following vaccination with the Takahashi strain of Rubella vaccine. Mice were injected intraperitonealy with Rubella virus and PBS and 7, 10 or 14 days later, spleen cells were separated and cultured with varying doses of virus, con A or only the medium. ELISA assays were performed on supernatants for measurement of IL-4, INF-gamma and IL-5. LTT (Lymphocyte Transformation Test) was also performed. The data indicate variation in cytokine patterns during the time periods after vaccination. On day 7 a type 1 pattern was observed. The LTT response was also indicative of CMI (Cell Mediated Immunity) response on the 7th and 14th days while a transient suppression on day 10 was observed. These results indicate a time dependent cytokine response with variation ultimately leading o a dominant type 1 (Ti) cytokine response.
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PMID:Murine cytokine patterns following rubella vaccination. 1730 62


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