Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P30536 (PBS)
9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influx of monocytes and neutrophils into the inflamed tissue could be an important aspect in the pathogenesis of inflammatory bowel disease (IBD). A membrane protein involved in the monocyte/neutrophil adherence to endothelium is CD11b/CD18 or alpha M beta 2 (complement receptor type 3 = CR3). In the present study the role of CD11b/CD18 in experimental IBD was studied by treatment with ED7 and OX42, two MoAbs against CD11b/CD18. Colitis was induced in rats by a single, rectal administration of 30 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol 30%. Two hours before and 3 days after induction of colitis, the animals were given an i.v. dose of 0.5 mg of either ED7 or OX42 in 1 ml PBS. Controls received PBS or an irrelevant MoAb. Four days after the last treatment with the antibodies, the rats were killed, and macroscopic damage scores of the colon were determined. Macrophages and granulocytes were studied by immunohistochemistry and quantified by Interaktives Bild Analysen System (IBAS), and myeloperoxidase (MPO) activity in colonic tissue was measured. After treatment with ED7 and OX42 the mean damage score of the colon was reduced from 4.2 in IBD animals to 1.0 and 1.3, respectively. Smaller areas of ulcerations and a decrease in the number of ulcerations were observed compared with PBS-treated rats. Furthermore, the amount of infiltrating monocytes and leucocytes in the submucosa was enormously reduced, as well as MPO activity in the colonic tissue. These results show that treatment with MoAbs against CD11b/CD18 reduces clinical signs of experimental IBD in rats by a partial blockade of infiltrating macrophages and granulocytes.
...
PMID:Anti-CD11b/CD18 antibodies reduce inflammation in acute colitis in rats. 764 20

The objective of this study was to quantify E-selectin surface expression in the colon as well as other tissues in a CD4(+) T-cell model of chronic colitis in mice using the newly developed dual radiolabel monoclonal antibody technique. Male SCID mice were reconstituted with either 5 x 10(5) CD4(+) CD45RB(low) or CD45RB(high) T-cells isolated from normal CB-17 donor mouse spleens and subsequently monitored for clinical signs of colitis. We found that animals injected with CD45RB(high) but not CD45RB(low) T-cells nor PBS developed colitis at 6-8 weeks following reconstitution as assessed by loss of body weight, development of loose stools and/or diarrhea, and histopathology. Concurrent with the onset of distal bowel inflammation was enhanced expression of E-selectin compared to SCID mice injected with PBS or reconstituted with CD45RB(low) T-cells, both of which did not develop colitis. We also observed significant increases in E-selectin expression in cecum, small intestine, mesentery, and liver of colitic mice. Our data confirm that reconstitution of SCID mice with CD45RB(high) but not CD45RB(low) T-cells induces chronic colitis and demonstrate that this chronic colitis is associated with enhanced expression of an endothelial cell-specific adhesion molecule. Furthermore, our studies demonstrate that reconstitution of SCID mice with CD45RB(high) T-cells enhances E-selectin expression in a variety of tissues distant from the site of active inflammation.
...
PMID:E-Selectin expression in a murine model of chronic colitis. 1067 41

Homeostasis between indigenous intestinal flora and host response may be broken in inflammatory bowel disease. The present study explores whether repeated oral administration of intestinal flora antigens can protect mice against dextran sodium sulphate (DSS)-induced colitis. Sonicates of Gram-positive, Gram-negative, or anaerobic resident bacteria isolated from mouse intestinal flora were fed to BALB/c mice by gastric gavage, with or without cholera toxin. After four weekly doses of 1 mg of these antigen preparations (or of PBS as control), DSS colitis was induced. One week later colitis was evaluated by clinical scores and histology. Mice fed a pool of the three sonicates had decreased inflammation scores (5 (1-14); median (range)) compared with PBS-fed control animals (15 (7-19); P < 0.05). Decreased inflammation was observed in mice fed anaerobic bacteria antigens (7 (6-11); P < 0.05 versus control), but not in mice fed a pool of Gram-positive and -negative sonicates (16 (12-16)). Inflammation scores of mice fed antigens with cholera toxin were similar to those of PBS-fed control animals. DSS-induced colitis can be suppressed by oral administration of normal intestinal flora antigens containing anaerobes.
...
PMID:Oral administration of antigens from intestinal flora anaerobic bacteria reduces the severity of experimental acute colitis in BALB/c mice. 1075 62

The transfer of genes encoding immunomodulatory proteins to the intestinal mucosa is a promising new approach to the treatment of Crohn's disease (CD). This study investigates the therapeutic efficacy of an adenoviral vector encoding IL-10 (AdvmuIL-10) in experimental colitis. BALB/c mice were treated with a single intravenous injection of AdvmuIL-10, empty cassette virus (Adv0) or PBS prior to the induction of trinitrobenzene sulphonic acid (TNBS) colitis. AdvmuIL-10 treatment prevented the severe loss of body weight associated with TNBS administration. In addition, AdvmuIL-10 therapy led to a significant reduction in both stool markers of inflammation (IL-1beta and TNFR-II) and acute phase response (serum amyloid protein). Finally, the histological scores of mice with TNBS colitis treated with AdvmuIL-10 were significantly lower than Adv0- or PBS-treated controls. The therapeutic efficacy of AdvmuIL-10 was associated with a decrease in the IFN-gamma and IL-6 levels detected in colonic homogenates from mice with TNBS colitis, whereas no effect was observed on cytokine release from stimulated systemic lymphocytes. Thus, AdvmuIL-10 is an effective therapy in the TNBS model of colitis. Gene therapy strategies using adenoviral vectors encoding IL-10 may prove to be a potent therapy for chronic inflammatory conditions such as CD.
...
PMID:IL-10 gene therapy prevents TNBS-induced colitis. 1245 86

Recent studies of murine models of mucosal inflammation suggest that, whereas some kinds of bacterial microflora are inducers of disease, others, known as probiotics, prevent disease. In the present study, we analyzed the regulatory cytokine and cell response to probiotic (VSL#3) administration in the context of the Th1 T cell colitis induced by trinitrobenzene sulfonic acid treatment of SJL/J mice. Daily administration of probiotics for 3 wk to mice during a remission period between a first and second course of colitis induced by trinitrobenzene sulfonic acid, resulted in a milder form of recurrent colitis than observed in mice administered PBS during this same period. This protective effect was attributable to effects on the lamina propria mononuclear cell (LPMC) population, because it could be transferred by LPMC from probiotic-treated mice to naive mice. Probiotic administration was associated with an early increase in the production of IL-10 and an increased number of regulatory CD4+ T cells bearing surface TGF-beta in the form of latency-associated protein (LAP) (LAP+ T cells). The latter were dependent on the IL-10 production because administration of anti-IL-10R mAb blocked their appearance. Finally, the LAP+ T cells were essential to the protective effect of probiotics because administration of anti-IL-10R or anti-TGF-beta at the initiation of recurrent colitis induction or depletion of LAP+ T cells from LPMC abolished the latter's capacity to transfer protection to naive recipients. These studies show that probiotic (VSL#3) administration during a remission period ameliorates the severity of recurrent colitis by inducing an immunoregulatory response involving TGF-beta-bearing regulatory cells.
...
PMID:Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. 1574 54

Our study examined whether repeated preventive oral administration of live probiotic bacterial strains Escherichia coli O83:K24:H31 (Ec O83), Escherichia coli Nissle 1917 O6:K5:H1 (Ec Nis) and Lactobacillus casei DN 114001 (Lc) can protect mice against dextran sodium sulfate (DSS)-induced colitis. A significant decrease in average symptom score was observed in Ec O83-, Ec Nis- and Lc-pretreated group (p < 0.05). Significant differences in body mass loss between Lc pretreated mice with DSS-induced colitis were found when compared with nontreated mice (p < 0.05). PBS pretreated mice had a significantly shorter colon than Ec O83-, Ec Nis- and Lc-pretreated mice (p < 0.05). Administration of Lc significantly decreased the severity of DSS induced histological marks of inflammation (p < 0.05). A significant difference (p < 0.05) was also found in specific IgA level against given probiotic in enteral fluid between colitic mice and healthy mice pretreated with Ec 083 and Ec Nis.
...
PMID:Oral administration of probiotic bacteria (E. coli Nissle, E. coli O83, Lactobacillus casei) influences the severity of dextran sodium sulfate-induced colitis in BALB/c mice. 1717 71

Cow milk contains a large amount of an immunoregulatory cytokine, transforming growth factor-beta (TGFbeta). The present study investigated whether commercially available pasteurized cow milk retains TGFbeta activity both in vitro and in vivo. Some commercial cow milk increased TGFbeta/Smad-responsive reporter activity and induced Smad2 phosphorylation and the transcription of the TGFbeta/Smad target genes TGFbeta itself and Smad7 in vitro. Mice treated orally with 500 microL of cow milk containing TGFbeta (3 microg/L) daily for 2 wk had increased phosphorylation of Smad2 and TGFbeta and Smad7 mRNA expression in the intestine. These mice also had significantly greater serum TGFbeta concentrations than the mice treated orally with PBS. Furthermore, oral administration of 500 microL of cow milk containing TGFbeta (3 microg/L) daily for 2 wk before the induction of dextran sodium sulfate colitis and lipopolysaccharide-induced endotoxemia ameliorated tissue damage and mortality, respectively, in mice. These in vivo effects of cow milk were abrogated by the simultaneous administration of TGFbeta type I receptor kinase inhibitor with the cow milk, and they were not observed after the oral administration of cow's milk containing little TGFbeta. In humans, 1 oral challenge of 10 mL/kg cow milk containing TGFbeta (3 microg/L) increased the plasma TGFbeta concentrations at 4 h after the challenge. Thus, some commercially available pasteurized cow milk retains TGFbeta activity, which may be able to provide protection against experimental colitis and endotoxemia associated with increased intestinal and circulating TGFbeta levels.
...
PMID:Transforming growth factor-beta activity in commercially available pasteurized cow milk provides protection against inflammation in mice. 1905 55

The role of interleukin 25 (IL-25) in a number of human diseases still has not been extensively studied, here we attempt to evaluate the role of recombinant IL-25 (rIL-25) in the development of dextran sulfate sodium (DSS)-induced experimental colitis. Acute colitis was induced in female C57BL/6 mice by oral administration of 2.5% DSS in drinking water ad libitum. At the same time as the start of DSS exposure, mice were injected intraperitoneally with 0.4 microg of rIL-25 or PBS. Then disease activity index (DAI), histological changes and survival rate were observed. The levels of IL-17, IL-23, and TGF-beta1 in colon tissues were determined by ELISA, and the production of IL-17 by CD4(+)/CD8(+) T cells was detected by intracellular flow cytometry. In contrast to the DSS treated mice, DSS + rIL-25 treated mice displayed a lower DAI, limited histological changes and prolonged survival. The levels of IL-23 and TGF-beta1 were significantly elevated in the DSS + rIL-25 treated mice compared to the DSS treated mice. There was no significant difference in the production of IL-17 in colon tissues and CD4(+)/CD8(+) T cells between the DSS + rIL-25 treated mice and DSS treated mice. Our findings suggest the role of IL-25 in inhibiting development and progression of acute colitis in DSS-induced mouse colitis model.
...
PMID:Inhibitory effect of recombinant IL-25 on the development of dextran sulfate sodium-induced experimental colitis in mice. 1911 8

Inflammatory bowel disease (IBD) represents a group of chronic inflammatory diseases characterized by inflammation and relapsing gastrointestinal disorders. Recent studies have shown that Th17 cells, which are well known as key mediators of chronic inflammation, have a pivotal role in onset and development of IBD in humans and mice, alike. In recent years, it has been reported that IL-27, which is an IL-12-related heterodimeric cytokine consisting of EBI3 and p28 subunits, act directly on naive T cells to suppress the differentiation of Th17 cells. However, effects of exogenous IL-27 on the IBD are not well elucidated. To clarify the suppressive effect of IL-27 treatment on IBD, we applied the flexible linking method to EBI3 and p28 subunits and generated a single-chain human IL-27 (scIL-27). scIL-27 inhibited xenogenic mouse Th17 cell differentiation in vitro, indicating that scIL-27 also acts in mouse immune systems. In a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse acute colitis model, subcutaneous scIL-27 treatment significantly improved the colon length, extent of necrosis, and ulceration and thickened epithelium and several pathological scores in a dose-dependent manner. scIL-27 clearly suppressed several inflammatory cytokines, including IL-17, in inflamed colon, except for anti-inflammatory cytokine IL-10. The mesenteric lymph node cells from scIL-27-treated mice also exhibited a reduced inflammatory response and, furthermore, a lower population of Th17 cells than those of PBS-treated mice. Finally, we showed the therapeutic efficacy of scIL-27 on TNBS-induced colitis even after active colitis was established. These results suggest new possible therapeutic approaches for IBD, including disorders such as Crohn's disease and ulcerative colitis.
...
PMID:Treatment with IL-27 attenuates experimental colitis through the suppression of the development of IL-17-producing T helper cells. 2119 26

Liposome-encapsulated corticosteroids have shown to exert strong beneficial effects in inflammatory diseases, such as arthritis and cancer. To extend the clinical applicability of these potent nanomedicines, the therapeutic effect of dexamethasone phosphate loaded long-circulating liposomes (LCL-DXP) was evaluated in animal models of multiple sclerosis (MS) and Crohn's disease (CD). In mice with experimental autoimmune encephalitis (EAE), a model for MS, treatment with LCL-DXP, but not free DXP, resulted in a decrease in disease activity when compared to PBS treated mice. In contrast, in mice with chronic DSS-induced colitis, a model for CD, treatment with LCL-DXP did not induce an improvement, but in fact worsened the fecal blood loss after treatment, indicating an aggravation of the disease. It is hypothesized that modulation of macrophage polarization towards a M2 phenotype underlies the efficacy of corticosteroid-based drug delivery systems, which is supported by the presented data. On the one hand, M1 polarized macrophages are part of the pathogenesis of MS; the modulation to M2-polarization by LCL-DXP is therefore beneficial. On the other hand, M1-polarized intestinal macrophages fulfill a protective and inflammation-suppressing role in intestinal homeostasis; changing their phenotype to M2 causes reduced protection to invading microorganisms, leading to a more severe intestinal inflammation. These findings therefore indicate that the interplay between the specific phenotype of macrophages and the specific inflammatory context of the inflammatory disease in question may be an important determining factor in the therapeutic applicability of liposomal corticosteroids in inflammatory disease.
...
PMID:Macrophages and liposomes in inflammatory disease: friends or foes? 2123 59


1 2 3 4 Next >>

---