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)

Systemic lupus erythematosus (SLE)-prone female MRL-lpr / lpr (MRL-lpr) mice were treated with mouse or rat IFN-gamma under different experimental conditions, both prophylactically in 6- to 8 week-old animals and therapeutically in 12- to 18-week-old SLE-affected mice. It was found that IFN-gamma heterogeneously modulated the course of the disease in MRL-lpr mice. When administered prophylactically, IFN-gamma favorably modulated the histological, serological and clinical signs of the disease. Relative to untreated or PBS-treated control animals, the MRL-lpr mice which received IFN gamma were virtually free of inflammatory infiltration of the kidneys and the lungs, had lower levels of azotemia with reduction of both circulating IgG1, IgG2a and IgG3 and anti-double strand (ds) and single strand (ss) DNA antibodies, milder skin vasculitis, significantly reduced enlargement of their lymph nodes and lower weight of the spleens. IFN-gamma also lowered the rate of mortality of MRL-lpr mice. In contrast to these findings, therapeutically administered IFN-gamma worsened the course of the disease in MRL-lpr mice, which exhibited increased proteinuria, higher levels of IgG2a and IgG3 and anti-ds and -ss DNA antibodies, more aggressive nephritis and died at an earlier age than PBS-treated control mice. The dichotomic effect of IFN-gamma on disease manifestation in MRL-lpr mice offers new insights into the complex role of this cytokine in the regulation of systemic autoimmunity such as SLE.
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PMID:Dichotomic effects of IFN-gamma on the development of systemic lupus erythematosus-like syndrome in MRL-lpr / lpr mice. 1067 Nov 99

We have previously shown that vaccination of BALB/c mice with a combination of BCG plus killed Leishmania promastigotes, applied by the i.p. route 10 and 3 days before Trypanosoma cruzi inoculation, prolonged their survival and decreased their parasitaemia. In the present study we show that the BCG-Leishmania vaccine induced higher levels of circulating IFN-gamma in acute and chronic infection of mice [on day 25 and 40 post-infection (p.i.) respectively], in comparison to unvaccinated animals (PBS-treated). Though the IFN-gamma mRNA content of spleen cells of vaccinated and infected mice (on day 25 p.i.) was similar to that of unvaccinated animals, the BCG-Leishmania vaccine enhanced significantly the production of IFN-gamma by spleen cells stimulated with T. cruzi antigens. This effect was observed to a lower extent in BCG- and Leishmania-treated mice. The BCG-Leishmania vaccine reduced the expression of the IL-10 mRNA of splenocytes as soon as day 12 p.i., before the peak parasitaemia. Such this effect was not observed in BCG- or Leishmania-treated animals. On day 25 p.i., the BCG plus Leishmania- or BCG-treatment of mice abolished the capacity of spleen cells to produce IL-10 in response to T. cruzi antigens. The levels of mIL-4 RNA and protein production were not modified in any group of mice. T. cruzi infection in BCG-Leishmania-vaccined mice stimulated an early and high production of IL-12 transcripts in spleen cells during the acute phase of the infection, that was prolonged during the chronic phase of infection. This effect was weaker or absent in BCG- and Leishmania-treated animals, respectively. These results indicate that the BCG-Leishmania vaccine stimulates the production of IL-12 and IFN-gamma, but inhibits that of IL-10 and is without effect on IL-4 when mice are infected with T. cruzi. This highlights the key role of endogenously produced IFN-gamma, IL-10 and IL-12 in the control of T. cruzi acute and chronic infection in mice and the favorable modulation of their balance by a vaccination combining BCG and Leishmania.
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PMID:IFN-gamma, IL-4, IL-10 and IL-12 gene expression in BCG-Leishmania vaccination of Trypanosoma cruzi-infected mice. 1069 30

We have studied the effects of either exogenously-administered interferon (IFN-)gamma or of a nonimmunogenic mouse IFN-gamma receptor-Immunoglobulin (IFN-gamma R-Ig) fusion protein on the development of Concanavalin (Con)A-induced hepatitis in NMRI mice. PBS-treated control mice injected with 20 mg/kg ConA developed classical serological and histological signs of hepatitis with elevation of transaminases in the blood and infiltration of the liver by mononuclear cells and neutrophils. Treating the mice with rat IFN-gamma 24 h prior to and 1 h after ConA-challenge markedly exacerbated these signs of hepatitis in a dose-dependent fashion. Moreover, mice injected with lower, non hepatitogenic, doses of ConA (10, 5 mg/kg) became fully susceptible to develop hepatitis upon similar treatment with IFN-gamma. Concordantly, ConA-induced hepatitis was abrogated by either IFN-gamma R-Ig fusion protein or anti-IFN-gamma mAb. These data provide further evidence for the central pathogenetic role of endogenous IFN-gamma in ConA-induced hepatitis and demonstrate the feasibility to prevent disease development by means of a non immunogenic IFN-gamma R-Ig fusion protein.
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PMID:Essential pathogenetic role for interferon (IFN-)gamma in concanavalin A-induced T cell-dependent hepatitis: exacerbation by exogenous IFN-gamma and prevention by IFN-gamma receptor-immunoglobulin fusion protein. 1080 11

IL-18 expression has recently been detected in rheumatoid arthritis (RA) synovial membrane. We investigated the mechanisms by which IL-18-induced collagen-induced arthritis in DBA/1 mice primed intradermally with type II bovine collagen in IFA and boosted i.p. 21 days later with CII in saline. Mice were injected i.p. with rIL-12, rIL-18, or both (100 ng) during days -1 to 4 and again on days 20-24. Control mice received PBS. Mice treated with IL-12 or IL-18 alone developed significantly higher incidence and more severe disease compared with controls. These were elevated further by combination treatment with IL-12 and IL-18. The cytokine treatments led to markedly enhanced synovial hyperplasia, cellular infiltration, and cartilage erosion compared with controls. Cytokine-treated mice produced significantly more IFN-gamma, TNF-alpha, and IL-6 than the controls. Interestingly, IL-18-treated mice produced more TNF-alpha and IL-6, but less IFN-gamma, compared with mice treated with IL-12. Furthermore, splenic macrophages from DBA/1 mice cultured in vitro with IL-18, but not IL-12, produced substantial amounts of TNF-alpha. Mice treated with IL-18 or IL-18 plus IL-12 produced markedly more IgG1 and IgG2a anti-collagen Ab compared with controls, whereas IL-12 treatment only led to an enhanced IgG2a response. Together these results demonstrate that IL-18 can promote collagen-induced inflammatory arthritis through mechanisms that may be distinct from those induced by IL-12.
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PMID:Combined effects of IL-12 and IL-18 on the induction of collagen-induced arthritis. 1084 7

We review our methods for definition and phenotypical characterisation of normal and activated rat monocytes. To obtain a comprehensive sample of all blood monocytes including cells from the marginal pool of the blood stream, we extensively perfuse the extrapulmonary circulation with cold PBS/EDTA. Normal rat monocytes are isolated from untreated specified pathogen-free male LEW rats. In vivo activated monocytes are investigated after three days of infusion of recombinant IFN-gamma or during acute renal allograft rejection. Rat monocytes are defined by reactivity with mAbs ED1 and ED9, detecting a lysosomal membrane antigen and a member of the signal-regulatory protein family, respectively, as well as by expression of CD11b. Concomitantly rat monocytes are characterized by the absence of CD5, the absence of the B cell form of CD45R, and the absence of reactivity with mAb RP-1. The majority of the monocytes from untreated LEW rats are CD4+, CD11a(high), CD18high, CD43high, CD62-L-, CD161-, and MHC class II-. Upon stimulation of the immune system in vivo, a second monocyte population increases in number. These cells have a larger diameter and an increased granularity. They are CD4-, CD11a(int), CD18int, CD43low, CD62-L+, CD161int, and MHC class II+. Although some reagents are not yet available (e.g. antibodies against rat CD14 and CD16), rat monocytes can be defined and their state of activation can be characterized. The functionally important population of monocytes, which have already marginated, is accessible by perfusion and relatively high monocyte numbers are isolated per rat. As specified pathogen-free rats are available and numerous experimental systems involving acute or chronic inflammation have been established in rats, differentially activated monocytes may be investigated. The rat is thus a suitable experimental animal for basic research on monocytes.
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PMID:Monocytes in the rat. 1087 93

In mice, individual dietary omega-3 polyunsaturated fatty acids n-3 (PUFA) were found to be sufficient to effect the changes in circulating interleukin (IL)-12 and interferon (IFN)-gamma levels that were previously seen in fish oil-fed mice. Weanling female C3H mice were fed one of five experimental diets. All five diets met all known nutritional requirements for mice and differed only in the fat source. After 4 weeks, mice were challenged with live Listeria monocytogenes or sterile PBS. Twenty-four hours after infection, n-3 PUFA-fed mice had significantly lower circulating IL-12 p70 and IFN-gamma than mice fed the control diet (P<.01). In addition, splenic cytokine mRNA for IL-12 p40, tumor necrosis factor-alpha, and IL-1beta were lower in infected mice fed n-3 PUFA-containing diets than in mice fed the olive oil ethyl esters control diet. The reduction of IL-12 and IFN-gamma production by n-3 PUFA may have important implications for host infectious disease resistance.
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PMID:Consumption of eicosapentaenoic acid and docosahexaenoic acid impair murine interleukin-12 and interferon-gamma production in vivo. 1094 84

Mucosal administration of low doses of myelin basic protein (MBP) peptide 68-86 (MBP 68-86) or anti-inflammatory cytokine IL-10 effectively prevented experimental allergic encephalomyelitis (EAE), but failed to suppress the disease if given after 7 days postimmunization (p.i.), i.e., after T cell priming had occurred. We anticipated that combined administration of autoantigen and IL-10 can treat incipient EAE. Lewis rats with EAE actively induced with MBP 68-86 and complete Freund's adjuvant received 120 microg MBP 68-86 + 200 ng IL-10 per rat per day from day 7 p.i. and for 5 consecutive days. These rats showed later onset, lower clinical scores, less body weight loss, and shorter duration of EAE than rats receiving MBP 68-86 or IL-10 only or PBS. EAE amelioration was associated with decreased infiltration of ED1(+) macrophages and CD4(+) T cells within the central nervous system and with decreased proliferative responses of lymph node cells, indicating that combined administration of MBP 68-86 and IL-10 induced immune hyporesponsiveness. IFN-gamma secretion as well as IFN-gamma, TNF-alpha, IL-4, and IL-10 mRNA expression by lymph node MNC was down-regulated in the treated rats. Immune hyporesponsiveness, rather than immune deviation or regulatory mechanisms, seems to be responsible for the protection of EAE after autoantigen + IL-10 administration by the nasal route.
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PMID:Combined nasal administration of encephalitogenic myelin basic protein peptide 68-86 and IL-10 suppressed incipient experimental allergic encephalomyelitis in Lewis rats. 1096 38

Product R (Reticulose(TM)) is a peptide-nucleic acid immunomodulator with broad-spectrum antiviral activity that was recently shown to increase expression of mRNAs encoding the proinflammatory cytokines, IFN-gamma, IL-1beta, IL-6 and TNF-alpha. Since these cytokines induce expression of the chemokines, MIP-1alpha, MIP-1beta, RANTES, and SDF-1, all of which inhibit viral infectivity, we were interested to determine if Product R also alters chemokine expression. In addition, the finding, that Product R decreases HIV-1 RNA and extracellular p24 antigen in H9 T-lymphoma cells, suggested to us that this drug may block viral infection by reducing the expression of chemokine receptors on target cells. We have therefore utilized H9 cells to test the effects of Product R on expression of mRNAs encoding the chemokine receptors, CD4, CXCR4 and CCR5, as well as their ligands, IL-16, SDF-1, MIP-1alpha, MIP-1beta, and RANTES, by RT-PCR. We also assayed the effect of Product R on surface receptor expression by flow cytometry, and on the chemotactic activity of these cells towards the CXCR4 ligand, SDF-1, and the CCR5 ligands, MIP-1alpha and RANTES. H9 cells were cultured for 3-21 days in medium containing 5% or 10% Product R, or 5% or 10% PBS. We found that, compared to control cultures, cells cultured in media containing Product R expressed lower amounts of CXCR4 and CCR5 mRNA and surface antigen at all time points. Culture for 3 days in media containing Product R also reduced the ability of cells to migrate towards 10-20 ng/ml SDF-1 and 100-250 ng/ml RANTES. In contrast, Product R had no effect on the expression of CD4 mRNA and receptor protein, or on expression of IL-16 mRNA. These findings suggest that Product R may have clinical efficacy in HIV-1-infected patients by downregulating viral coreceptors on target T-cells.
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PMID:CXCR4 and CCR5 expression by H9 T-cells is downregulated by a peptide-nucleic acid immunomodulator. 1106 99

Monocyte chemoattractant proteins-1 and -5 have been implicated as important mediators of allergic pulmonary inflammation in murine models of asthma. The only identified receptor for these two chemokines to date is the CCR2. To study the role of CCR2 in a murine model of Ag-induced asthma, we compared the pathologic and physiological responses of CCR2(-/-) mice with those of wild-type (WT) littermates following immunization and challenge with OVA. OVA-immunized/OVA-challenged (OVA/OVA) WT and CCR2(-/-) mice developed significant increases in total cells recovered by bronchoalveolar lavage (BAL) compared with their respective OVA-immunized/PBS-challenged (OVA/PBS) control groups. There were no significant differences in BAL cell counts and differentials (i.e., macrophages, PMNs, lymphocytes, and eosinophils) between OVA/OVA WT and CCR2(-/-) mice. Serologic evaluation revealed no significant difference in total IgE and OVA-specific IgE between OVA/OVA WT mice and CCR2(-/-) mice. Lung mRNA expression and BAL cytokine protein levels of IL-4, IL-5, and IFN-gamma were also similar in WT and CCR2(-/-) mice. Finally, OVA/OVA CCR2(-/-) mice developed increased airway hyper-responsiveness to a degree similar to that in WT mice. We conclude that following repeated airway challenges with Ag in sensitized mice, the development of Th2 responses (elevated IgE, pulmonary eosinophilia, and lung cytokine levels of IL-4 and IL5) and the development of airway hyper-responsiveness are not diminished by a deficiency in CCR2.
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PMID:CC chemokine receptor-2 is not essential for the development of antigen-induced pulmonary eosinophilia and airway hyperresponsiveness. 1108

The damage of acetylcholine receptor (AChR) at neuromuscular junctions of experimental autoimmune myasthenia gravis (EAMG), an animal model of human MG, is mediated by B cells which require T cell help. The Th2 associated cytokine IL-10 suppresses production of cytokines released by Th1 cells and is considered for treatment of human autoimmune diseases. To evaluate the role of IL-10 in EAMG, rhIL-10 was administered daily to Lewis rats by the subcutaneous route starting at the day of immunization and continued for 7 weeks. IL-10 failed to abrogate EAMG at low dose (0.1 or 1 microg/day) and at the dose of 3 microg/day caused earlier onset and aggravated clinical signs of EAMG when compared to EAMG rats injected with PBS only. Although Th1 responses reflected by AChR-induced lymphocyte proliferation and levels of IFN-gamma secreting cells, as well as AChR-induced Th1 cytokine mRNA expression was suppressed, augmented IL-4 mRNA expression and AChR-specific B cell responses may play an important role in the failure of IL-10 to abrogate EAMG. This study implicates a critical precaution in planning immunotherapy of IL-10 in antibody-mediated autoimmune diseases, e.g. MG.
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PMID:Interleukin 10 aggravates experimental autoimmune myasthenia gravis through inducing Th2 and B cell responses to AChR. 1113 72


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