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)

RANTES (CC chemokine ligand 5) contributes to airway inflammation through accumulation of eosinophils, but the exact role of RANTES (CCL5) is not defined. C57BL/6 mice, sensitized by injection of ovalbumin (OVA) on Days 1 and 14, were challenged with OVA on Days 28, 29, and 30 (3 challenges, short-term-challenge model) or on Days 28, 29, 30, 36, 40, 44, and 48 (7 challenges, repeated-challenge model) and evaluated 48 h later. Anti-mouse RANTES was given intravenously, and recombinant mouse RANTES or PBS was given intratracheally. These reagents were given on Days 28, 29, and 30 in the short-term-challenge study and on Days 44 and 48 in the repeated-challenge study. After short-term challenge, there were no effects after administration of anti-RANTES or RANTES. In the repeated-challenge study, although control mice showed a decrease in airway hyperresponsiveness, administration of anti-RANTES sustained and enhanced airway hyperresponsiveness and increased goblet cell numbers. In contrast, administration of RANTES normalized airway function but reduced goblet cell numbers. IL-12 and IFN-gamma levels in BAL decreased in the anti-RANTES group and increased in the RANTES group. IFN-gamma-producing CD4 T cells in lung, and IFN-gamma production from lung T cells in response to OVA in the anti-RANTES group, were significantly decreased but were increased in the RANTES group. Anti-IFN-gamma, administered with RANTES, decreased the effects of RANTES on AHR after repeated challenge. These data indicate that RANTES plays a role in the regulation of airway function after repeated allergen challenge, in part through modulation of levels of IFN-gamma and IL-12.
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PMID:RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge. 1684 5

The human CXC chemokine, stromal cell-derived factor 1 (SDF-1alpha), is known to function in vitro as a chemotactic factor for lymphocytes, monocytes, and dendritic cells. In the context that dendritic cells are powerful antigen-presenting cells, we hypothesized that adenoviral gene transfer of SDF-1alpha to tumors might inhibit growth of preexisting tumors through attracting dendritic cells to the tumor. AdSDF-1alpha mediated the expression of SDF-1alpha mRNA and protein in A549 cells in vitro, and the supernatant of the AdSDF-1alpha-infected A549 cells showed chemotactic activity for dendritic cells. When syngeneic murine CT26 colon carcinoma tumors (BALB/c) and B16 melanoma and Lewis lung cell carcinoma (C57Bl/6) were injected with AdSDF-1alpha (5 x 10(8) plaque-forming units), there was an accumulation of dendritic cells and CD8(+) cells within the tumor and significant inhibition of tumor growth compared with tumors injected with PBS or AdNull (control vector). The injection of AdSDF-1alpha into tumors induced the inflammatory enlargement and the accumulation of dendritic cells in the draining lymph node. Intratumoral AdSDF-1alpha administration elicited tumor-specific CTLs and adoptive transfer of splenocytes from AdSDF-1alpha-treated mice resulted in the elongation of survival after tumor challenge. Interestingly, in wild-type and CD4(-/-) mice but not in CD8(-/-) mice, AdSDF-1alpha inhibited the growth of the tumor. These observations suggest that adenoviral gene transfer of SDF-1alpha may be a useful strategy to accumulate dendritic cells in tumors and evoke antitumor immune responses to inhibit tumor growth.
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PMID:Adenoviral gene transfer of stromal cell-derived factor-1 to murine tumors induces the accumulation of dendritic cells and suppresses tumor growth. 1658 75

Interleukin 2 (IL)-2 induces antitumor immunity and clinical responses in melanoma and renal cell carcinoma. However, IL-2 also increases the number of CD4(+)CD25(+) regulatory T (Treg) cells that suppress antitumor immune responses. The aim of the present study was to elucidate the effect of depletion of Treg cells on IL-2-induced antitumor immunity. IL-2-transfected mouse colon adenocarcinoma (MC38/IL-2) cells were implanted subcutaneously or intrahepatically into male C57BL/6 mice, and tumor growth and the proportion of tumor-infiltrating lymphocytes with Treg-cell depletion in response to treatment with anti-CD25 monoclonal antibody (PC61) were determined. In mice treated with phosphate-buffered saline, 40-60% of MC38/IL-2 tumors were rejected. In contrast, all MC38/IL-2 tumors were rejected in mice treated with PC61. The number of tumor-infiltrating CD8(+) T cells in mice treated with PC61 was approximately twice that in mice treated with PBS. The numbers of tumor-infiltrating CD4(+) and natural killer cells were also increased significantly. To test the antimetastatic effects of IL-2 treatment in combination with Treg-cell depletion, human recombinant IL-2 (rIL-2) and PC61 were administered to mice implanted with MC38/mock cells in the spleen, and hepatic metastasis was investigated. The average liver weight in mice treated with rIL-2 plus PC61 was 1.04 +/- 0.03 g, less than that in mice treated with rIL-2 (2.04 +/- 0.51 g) or PC61 alone (1.81 +/- 0.38 g). We conclude that IL-2-induced antitumor immunity is enhanced by Treg-cell depletion and is due to expansion of the tumor-infiltrating cytotoxic CD8(+) T-cell population.
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PMID:Depletion of CD4+CD25+ regulatory T cells enhances interleukin-2-induced antitumor immunity in a mouse model of colon adenocarcinoma. 1727 31

Graft-versus-host disease (GVHD) continues to be a serious complication that limits the success of allogeneic bone marrow transplantation (BMT). Using IL-7-deficient murine models, we have previously shown that IL-7 is necessary for the pathogenesis of GVHD. In the present study, we determined whether GVHD could be prevented by antibody-mediated blockade of IL-7 receptor alpha (IL-7Ralpha) signaling. C57/BL6 (H2K(b)) recipient mice were lethally irradiated and underwent cotransplantation with T-cell-depleted (TCD) BM and lymph node (LN) cells from allogeneic BALB/c (H2K(d)) donor mice. Following transplantation, the allogeneic BMT recipients were injected weekly with either anti-IL-7Ralpha antibody (100 mug per mouse per week) or PBS for 4 weeks. Anti-IL-7Ralpha antibody treatment significantly decreased GVHD-related morbidity and mortality compared with placebo (30% to 80%). IL-7Ralpha blockade resulted in the reduction of donor CD4(+) or CD8(+) T cells in the periphery by day 30 after transplantation. Paradoxically, the inhibition of GVHD by anti-IL-7Ralpha antibody treatment resulted in improved long-term thymic and immune function. Blockade of IL-7R by anti-IL-7Ralpha antibody resulted in elimination of alloreactive T cells, prevention of GVHD, and improvement of donor T-cell reconstitution.
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PMID:Prevention of graft-versus-host disease by anti IL-7Ralpha antibody. 1759 35

A mouse model for allergic airway inflammation involving ovalbumin (OVA) sensitization and challenge has been developed that reproduces hallmark features of human asthma and has provided valuable insight into the mechanisms by which this disease occurs. Cellular infiltrate in lungs of mice used in this model have conventionally been evaluated using histological examination of tissue sections and light microscopic analysis of lung lavage samples. As an alternative or complementary approach for characterizing cellular infiltrate, we developed a multicolor fluorescence-activated cell sorter (FACS) method involving the simultaneous detection of seven different markers on lung cell suspensions: CD4, CD8, B220, CD11b, Gr-1, CD49b, and FcepsilonRI. Only some of these cell types increased in OVA-challenged mice compared to PBS controls, including the CD4(+), B220(+), CD11b(+), and FcepsilonRI(+) groups. We also examined subpopulations of cells for coexpression of these markers and dissected heterogeneous populations as further evaluation procedures to characterize the cellular infiltrate resulting from OVA challenge. Finally, we combined FACS with real-time PCR to analyze certain cell types in terms of mRNA levels for factors involved in asthma, including GATA-3 and IL-1beta. Overall, these FACS-based techniques provide a powerful approach for analyzing cellular profiles in lung tissue from mice used in the mouse model of asthma and may also prove valuable in evaluating cellular infiltrates for other models of inflammation and immune responses.
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PMID:A new approach for analyzing cellular infiltration during allergic airway inflammation. 1782 15

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

The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [n = 41], PRCV/DEX [n = 41], mock/PBS [n = 23], and mock/DEX [n = 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 x 10(7) PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2(+), CD3(+), CD4(+), and CD8(+) T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-gamma)-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-gamma-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects.
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PMID:Altered pathogenesis of porcine respiratory coronavirus in pigs due to immunosuppressive effects of dexamethasone: implications for corticosteroid use in treatment of severe acute respiratory syndrome coronavirus. 1794 63

Expression of MCP-1 in the central nervous system (CNS) is associated with various neuroinflammatory diseases, including multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In this study, we found that MCP-1 was decreased in the CNS but increased in the gut following oral administration of myelin basic protein (MBP) correlating with protection from EAE. To study the trafficking and the fate of T cells during oral tolerance, MBP-specific TCR transgenic (Tg) CD4(+) T cells were labeled using 5,6-carboxy-succinimidyl-fluorescein-ester (CFSE) and transferred intravenously to syngeneic B10.PL recipients before feeding with either MBP or PBS. We observed that the CFSE-labeled T cells traffic to the peripheral lymphoid tissue and the Peyer's patches (PP). The labeled T cells proliferate in vivo in both the lymph node and the PP 48h after MBP feeding, but the cells are maintained in the PP longer than in the LN. CFSE-labeled cells in the PP have high levels of CD69 and Fas expression which is accompanied by increased apoptosis after MBP feeding. Our observations suggest that oral administration of autoantigen induces an elevation of MCP-1 in the gut, early T cell trafficking and activation in the periphery and the PP, followed by deletion of autoreactive T cells in the PP.
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PMID:The Peyer's patch is a critical immunoregulatory site for mucosal tolerance in experimental autoimmune encephalomylelitis (EAE). 1800 71

Although B cells play a pathogenic role in the initiation of type 1 diabetes (T1D) in NOD mice, it is not known whether activated B cells can maintain tolerance and transfer protection from T1D. In this study, we demonstrate that i.v. transfusion of BCR-stimulated NOD spleen B cells into NOD mice starting at 5-6 wk of age both delays onset and reduces the incidence of T1D, whereas treatment initiated at 9 wk of age only delays onset of T1D. This BCR-activated B cell-induced protection from T1D requires IL-10 production by B cells, as transfusion of activated B cells from NOD.IL-10(-/-) mice does not confer protection from T1D. Consistent with this result, severe insulitis was observed in the islets of NOD recipients of transfused NOD.IL-10(-/-) BCR-stimulated B cells but not in the islets of NOD recipients of transfused BCR-stimulated NOD B cells. The therapeutic effect of transfused activated NOD B cells correlates closely with the observed decreased islet inflammation, reduced IFN-gamma production and increased production of IL-4 and IL-10 by splenocytes and CD4(+) T cells from NOD recipients of BCR-stimulated NOD B cells relative to splenocytes and CD4(+) T cells from PBS-treated control NOD mice. Our data demonstrate that transfused BCR-stimulated B cells can maintain long-term tolerance and protect NOD mice from T1D by an IL-10-dependent mechanism, and raise the possibility that i.v. transfusion of autologous IL-10-producing BCR-activated B cells may be used therapeutically to protect human subjects at risk for T1D.
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PMID:Intravenous transfusion of BCR-activated B cells protects NOD mice from type 1 diabetes in an IL-10-dependent manner. 1802 64

Surfactants like particles (SLP) are secreted by Intestinal epithelium. These particles have the ability to lower surface tension of intestinal epithelial cells and contain small amounts of surfactant specific proteins A, B, and D. In the intestinal lumen they are known to function as lubricants and/or as a vehicle to deliver digestive enzymes to the luminal fluid. These particles have been found to have the ability in binding of uropathogenic E.coli. But their immunological function is not known. The present study was designed to assess the role of the SLP in the regulation of immune response during Salmonella (S) typhimurium infection using a rat an enteric model. The animals were divided in four different groups including control (PBS), rats fed fat diet (corn oil), rats fed fat diet followed with S. typhimurium infection and rats with S. typhimurium infection alone. The Peyer's patches (PP), intraepithelial (IE) and lamina propria (LP) mononuclear cells were isolated from the above-mentioned groups. These mononuclear cells were then incubated in presence of S. typhimurium lysate alone, SLP alone and S. typhimurium lysate and SLP together. T cell markers CD4 and CD8, cytokines mainly pro-inflammatory ones including IFN-gamma, TNF-alpha, IL-12 etc were studied under such conditions. In addition histological studies were also carried out under these conditions. We report in this study that SLP plays an important role in modulating the cytokine level during infection. The pro-inflammatory cytokines were found significantly reduced in SLP induced diet along with the infection group compared to the infection group alone. Histopathological studies revealed the breakdown of duodenal villi after infection while only broadening of villi was observed in rats given corn oil induced SLP along with infection. These results suggested an important immuno-modulatory role for SLP during Salmonella infection.
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PMID:Immunoregulatory role of intestinal surfactant-like particles during Salmonella typhimurium infection. 1802 66


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