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)

Regulatory T (T(reg)) cells show promise for treating autoimmune diseases, but their induction to elevated potency has been problematic when the most optimally derived cells are from diseased animals. To circumvent reliance on auto-antigen reactive T(reg) cells, stimulation to vaccine antigens (Ags) may offer a viable alternative while maintaining potency to protect against proinflammatory diseases. Our Salmonella vaccine expressing colonization factor Ag I (CFA/I) possesses anti-inflammatory properties, evident by elevated Th2 cell responses, reduced inflammatory cell infiltrates in the Peyer's patches, and an absence of proinflammatory cytokine production by infected macrophages. Given these findings, we hypothesized whether this vaccine would be protective against experimental autoimmune encephalomyelitis (EAE). As such, Salmonella-CFA/I protected in both prophylactic and therapeutic paradigms against proteolipid protein (PLP(139-151))-mediated EAE in SJL mice. The protected mice showed significantly reduced clinical disease and subsequent resolution when compared to PBS-treated controls. Histopathological studies showed reduced demyelination and no inflammation of spinal cords when compared to PBS- or Salmonella vector-treated mice. To ascertain whether the observed immune deviation was in part supported by T(reg) cells, analysis revealed involvement of FoxP3(+) CD25(+) CD4(+) T cells. Adoptive transfer of induced TGF-beta (+) T(reg) cells from vaccinated mice showed complete protection against PLP(139-151) challenge, but not by naive T(reg) cells. Partial protection to EAE was also achieved by the adoptive transfer of CD25(-) CD4(+) T cells, suggesting that Th2 cells also contributed. Thus, these data show that T(reg) cells are induced by oral vaccination with Salmonella-CFA/I contributing to the efficacious treatment of autoimmune disease.
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PMID:Tolerance in the absence of autoantigen. 1789 47

Administration of autoantigen can be of value for prevention of autoimmune diabetes and it has been speculated that the control point of dendritic cells (DC) for the induction of peripheral tolerance may be highly relevant. We examined the properties of DC associated with immune suppression in NOD mice by insulin injection subcutaneously and the ability of which to suppress diabetes transfer by diabetogenic effector cells in secondary NOD-SCID recipients. Our data showed that the surface expressions of MHC II and CD86 on NOD-derived DC were increased after insulin treatment compared with those on PBS controlled mice. The dendritic cells with a mature phenotype and increased MLR stimulation adoptively transferred immune tolerogenic effects in secondary NOD-SCID mice, which were associated with significant greater IL-10, TGF-beta production and CD4(+)CD25(+)T differentiation from splenocytes compared with NOD-SCID control recipients. Moreover, treatment with DC remarkably decreased the incidence of diabetes in secondary recipients. These results suggest that a subtype of DC generated by insulin subcutaneous treated NOD mice confers potential protection from diabetes through polarizing the immune response towards a Th2 regulatory pathway.
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PMID:Insulin administration confers diabetes-preventive properties to NOD mice derived dendritic cells. 1807 57

CpG-oligodeoxynucleotides (CpG-ODN) are potent stimulators of the innate immune system. They promote a Th1-biased immune response with antineoplastic potential. We recently demonstrated antitumoral effects of CpG-ODN in murine transitional cell carcinoma (TCC) models. The purpose of the present work was to more precisely define the immunological nature of this immunotherapeutic approach to TCC.MB-49 TCC was established in female C57/Bl6 mice by intravesical tumor cell instillation after poly-L-lysine conditioning of the bladder (day 0) as described previously. Three groups of six mice were treated: intravesical instillation of 50 microl PBS on days 1, 3, 5, and 7 (group 1, untreated control); 10 nmol CpG 1668 on days 1, 3, 5, and 7 (group 2); and 10 nmol GpC 1668 on days 1, 3, 5, and 7 (group 3). Six native bladders served as no-treatment/no-tumor controls (group 4). Mice were sacrificed on day 11; bladders and draining lymph nodes were removed, and mRNA was prepared for quantitative real-time polymerase chain reaction. Samples were analyzed on a Bio-Rad iCycler for IL 10, TGF-beta, IL 12, and IFNgamma expression; threshold values were compared to beta-actin as housekeeping gene.Tumor take was 100%. Three animals in group 1 had to be sacrificed in advance due to rapid tumor progression. Relative cytokine expression was comparable in groups 1 and 4. IL-10, IL-12, TGF-beta, and IFNgamma were overexpressed in groups 2 and 3. CpG-ODN treatment of murine TCC results in overexpression of both classic Th1 cytokines (IL 12 and IFNgamma) and the Th2 marker IL 10. TGF-beta expression is increased as well. These phenomena are not induced by the growing TCC but by CpG-ODN therapy. They are accompanied by an objective clinical response, as we were able to show recently. Immunostimulatory DNA holds promise to be a novel therapeutic agent in TCC.
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PMID:[Immunostimulatory CpG oligodeoxynucleotides (CpG-ODN) in an orthotopic murine transitional cell carcinoma (TCC) model. Effect on local cytokine expression]. 1867 50

The acute phase response, an important aspect of innate immunity, leads to the production of acute phase proteins (APPs) in the liver which would consequently help restore homeostasis to the body. Here, we identified a novel cytokine, growth differentiation factor 15 (GDF15) from Japanese flounder. Three out of the 384 EST sequences derived from liver of Japanese flounder treated with formalin-killed Edwardsiella tarda showed significant homology with GDF of various species. After obtaining the full-length cDNA, the deduced amino acid sequence exhibited low identity (<30%) with GDF15s of higher vertebrates. The predicted ORF of JFGDF15 revealed a signaling peptide at the N terminal, a TGFbeta propeptide domain and a TGFbeta domain. The mature peptide domain of JFGDF15 contains an RXXR motif, a furin cleavage site, required for the release of the mature peptide and conserved amino acids, which are signature features of TGFbeta superfamily proteins. JFGDF15 mRNA transcripts were detected in fish, 6h post-injection with PBS. The transcripts were highly up-regulated in liver at 6h post-injection with formalin-killed E. tarda. Moreover, up-regulation of the transcripts was also observed at 12h post-injection with formalin-killed Streptococcus iniae.
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PMID:Growth differentiation factor 15, a novel acute phase response gene in Japanese flounder, Paralichthys olivaceus. 1905 42

Highly porous dextran-based hydrogels [in which various amounts (up to 16.6%, w/w) of a benzylaminated dextran (DMCB) exhibiting high affinity for TGFbeta1 was immobilized] were developed to achieve long-term retention of bioactive TGFbeta1 in situ. Unmodified hydrogels rapidly desorbed 80-90% compared with only 40-60% of the preloaded TGFbeta1 from the DMCB-modified hydrogels during a period of 21 days in PBS in vitro. TGFbeta1 release experiments (performed with high ionic strength solutions) indicated that formation of the complex between TGFbeta1 and functionalized hydrogels was governed by different interactions, depending on the degree of conjugation with DMCB: ionic interactions in the case of weakly conjugated matrices and nonionic interactions in highly conjugated matrices. Using cells containing a TGFbeta-sensitive luciferase reporter gene, weakly DMCB-modified hydrogels sequestered bioactive TGFbeta1 in situ, giving much higher, long-term signaling performance than highly functionalized hydrogels. Because these biocompatible functionalized hydrogels can provide long-term bioactive TGFbeta1, they could be used as scaffolds for cells to stimulate and regulate human tissue repair processes.
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PMID:Benzylaminated dextran-modified hydrogels: a long-term bioactive TGF-beta1 carrier. 1914 27

Chronic production of reactive oxygen and nitrogen species is an underlying mechanism of irradiation (IR)-induced lung injury. The purpose of this study was to determine the optimum time of delivery of an antioxidant and redox-modulating Mn porphyrin, MnTE-2-PyP(5+), to mitigate and/or treat IR-induced lung damage. Female Fischer-344 rats were irradiated to their right hemithorax (28 Gy). Irradiated animals were treated with PBS or MnTE-2-PyP(5+) (6 mg /kg/24 h) delivered for 2 weeks by sc-implanted osmotic pumps (beginning after 2, 6, 12, 24, or 72 h or 8 weeks). Animals were sacrificed 10 weeks post-IR. Endpoints were body weight, breathing frequency, histopathology, and immunohistochemistry (8-OHdG, ED-1, TGF-beta, HIF-1alpha, VEGF A). A significant radioprotective effect on functional injury, measured by breathing frequency, was observed for all animals treated with MnTE-2-PyP(5+). Treatment with MnTE-2-PyP(5+) starting 2, 6, and 12 h but not after 24 or 72 h resulted in a significant decrease in immunostaining for 8-OHdG, HIF-1alpha, TGF-beta, and VEGF A. A significant decrease in HIF-1alpha, TGF-beta, and VEGF A, as well as an overall reduction in lung damage (histopathology), was observed in animals beginning treatment at the time of fully developed lung injury (8 weeks post-IR). The catalytic manganese porphyrin antioxidant and modulator of redox-based signaling pathways MnTE-2-PyP(5+) mitigates radiation-induced lung injury when given within the first 12 h after IR. More importantly, this is the first study to demonstrate that MnTE-2-PyP(5+) can reverse overall lung damage when started at the time of established lung injury 8 weeks post-IR. The radioprotective effects are presumably mediated through its ability both to suppress oxidative stress and to decrease activation of key transcription factors and proangiogenic and profibrogenic cytokines.
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PMID:Early and late administration of MnTE-2-PyP5+ in mitigation and treatment of radiation-induced lung damage. 2009 48

Non-alcoholic steatohepatitis (NASH) is a progressive liver disease more commonly diagnosed in obesity. Therapeutic options to treat NASH are limited. Liver inflammation is a hallmark of NASH, and here it was tested whether the lipid mediator resolvin E1 (RvE1) and chemerin derived C15 peptide, which both exert potent anti-inflammatory activities, ameliorate NASH pathology. Male mice fed an atherogenic diet for 12 weeks, well described to induce NASH, received intraperitoneal injections of RvE1, C15 peptide or PBS as control for four days. Both treatments did not affect body weight or serum ALT. Liver triglycerides were neither reduced by the lipid nor the peptide. Hepatic expression of the macrophage marker F4/80 and the inflammatory mediators TNF and CCL2 was not changed. Further, fibrotic genes including TGFbeta, alphaSMA and CTGF were not affected by RvE1 or C15 injections. Serum adiponectin was comparable in the three groups. RvE1 and C15 are ligands of CMKLR1 whose expression was not reduced upon feeding the NASH inducing diet. This excludes low receptor levels as reason for therapeutic failure. In summary, current data demonstrate that RvE1 and chemerin derived C15 peptide do not ameliorate murine NASH.
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PMID:Resolvin E1 and chemerin C15 peptide do not improve rodent non-alcoholic steatohepatitis. 2568 56


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