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)

The immunologic and histologic changes associated with lung allograft rejection are believed to result from the presentation of donor lung alloantigens to recipient lymphocytes resulting in up-regulated Th1 lymphocyte activity. The ability of allogeneic lung immune cells to induce the pathologic and immunologic changes associated with acute lung allograft rejection are unknown. The current study determined whether allogeneic (C57BL/6, I-a(b)) bronchoalveolar lavage (BAL) cells (> or = 97% macrophages), when instilled into the lungs of recipient BALB/c mice (I-a(d)), induced the histology and immunology associated with acute lung allograft rejection. BALB/c mice received BAL cells from either C57BL/6 mice (allogeneic instillate) or BALB/c mice (autologous instillate) or PBS (control) by nasal insufflation weekly for 4 wk. Allogeneic BAL cells resulted in a lymphocytic bronchitis and vasculitis analogous to grade 1 to 2 lung allograft rejection. The mice given allogeneic instillates had a greater percentage of lymphocytes in the BAL fluid than those given autologous instillates. After instillation of allogeneic BAL cells, the Th1 cytokines, IL-2 and IFN-gamma (IFN-gamma), were produced locally in greater quantities and more frequently than Th2 cytokine IL-10. IL-4, another Th2 cytokine, was not detected. The local production of IgG1 and IgG2a, which are dependent on IL-4 and IFN-gamma, respectively, were increased. However, only IgG2a was deposited in the perivascular and peribronchiolar tissues. These data show that installation of allogeneic BAL cells into the airways of recipient mice induced up-regulated Th1 lymphocyte activity and caused the histologic changes associated with lung allograft rejection.
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PMID:Allogeneic bronchoalveolar lavage cells induce the histology of acute lung allograft rejection, and deposition of IgG2a in recipient murine lungs. 765 Apr 3

The effect of IL-4, IL-10, and TGF-beta on expression of procoagulant activity (PCA) and of surface-associated tissue factor (TF) by human monocyte-derived macrophages was determined. Monocytes were allowed to mature to macrophages in teflon bags, and were primed either in suspension cultures, or after subculturing in microtiter plates. PCA was determined in PBS-stimulated cells (constitutive PCA) or after stimulation with LPS for 6 hr. TGF-beta significantly reduced constitutive and LPS-induced PCA. This effect was associated with a reduction in surface-expressed TF, but was not correlated with TNF-alpha production in LPS-stimulated cells. The TGF-beta effect was seen both in suspension cultures and in adherent cultures. IL-10 strongly down-regulated LPS-induced PCA, an effect closely correlated with TNF production. It had a weaker, albeit significant effect on constitutive PCA, when tested on suspended cells, and PCA down-regulation was associated with reduction in TF surface expression. IL-4 reduced neither constitutive nor induced PCA in macrophages, and had little effect on TF surface expression, although it strongly down-regulated CD14 expression. Also in monocytes, IL-4 influenced TF expression to a lesser degree than IL-10 and TGF-beta. In the monocytoid cell line, THP-1, PCA/TF was down-regulated preferentially by TGF-beta. Our findings point to a complex cytokine-mediated regulation of PCA at the level of TF expression and possibly at additional levels.
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PMID:Transforming growth factor-beta and interleukin-10, but not interleukin-4, down-regulate procoagulant activity and tissue factor expression in human monocyte-derived macrophages. 790 94

Langerhans cells (LC) are Ag-presenting cells required for induction of primary immune responses in skin. After activation by Ag, LC express increased levels of MHC class II Ag, exhibit increased accessory cell activity, and migrate to regional lymph nodes where they stimulate T cells. One of the earliest manifestations of LC activation is the accumulation of increased amounts of IL-1 beta mRNA in LC within 15 min after exposure to contact allergens in vivo. To determine if enhanced IL-1 beta production by LC could be causally linked to epicutaneous sensitization, we injected IL-1 beta intradermally into the ears of BALB/c mice and extracted total epidermal RNA 4 h later. A quantitative reverse transcriptase-polymerase chain reaction technique was used to compare changes in IL-1 alpha, IL-1 beta, macrophage inflammatory protein 2, IL-10, TNF-alpha, and 1-A alpha chain mRNA signals caused by intradermally-injected IL-1 beta to those caused by intradermal IL-1 alpha or TNF alpha, or by topical application of the contact allergen trinitrochlorobenzene (3% TNCB). Intradermal injection of 25 ng IL-1 beta resulted in 5-to 100-fold enhancement of mRNA signals for IL-1 alpha, IL-1 beta, MIP-2, IL-10, TNF alpha, and class II I-A alpha, mimicking the changes caused by allergen. In contrast, injection of equivalent amounts of IL-1 alpha or TNF alpha did not significantly alter the epidermal cytokine pattern. Simulating the effects of topically applied TNCB, intradermally-injected IL-1 beta (but not IL-1 alpha or TNF alpha) also caused enhancement of LC MHC class II expression. In addition, LC derived from IL-1 beta-injected skin were 2 to 3 times more potent accessory cells in an anti-CD3 proliferation assay than LC from IL-1 alpha or sham-injected skin. Finally, injection of hamster anti-mIL-1 beta mAb into the skin prior to TNCB treatment completely prevented sensitization to this allergen, although injections of similar amounts of hamster anti-mIL-1 alpha mAb or PBS were without effect. Taken together, our data indicate that dendritic cell-derived IL-1 beta may be a critical molecule required for initiation of primary immune responses in skin.
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PMID:An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin. 847 27

We investigated the effects of IL-12 on a murine model of allergic lung inflammation. Administration of IL-12 was timed to interfere with either allergic sensitization (early dosage) or the hypersensitivity inflammatory response in the lung (late dosage), or both (early and late dosages). Comparisons of IL-12- and PBS-treated animals within each treatment group revealed several noticeable effects of IL-12. Early dosage, and the combination of early and late dosages, strikingly decreased ragweed-specific serum IgE, tracheal ring reactivity to acetylcholine, and BAL eosinophilia following allergen challenge. In contrast, late dosage had no effect on IgE levels and only a minimal effect on tracheal ring reactivity, but had a modest effect on recruitment of eosinophils. Early dosage down-regulated IL-5 and IL-10, but did not alter IL-4 or IFN-gamma expression. Late dosage down-regulated IL-5, up-regulated IL-10 and IFN-gamma, but did not change IL-4 expression. The combination of early and late dosage down-regulated IL-4, IL-5, and IL-10 expression, but increased IFN-gamma expression and production in the BAL cells and fluids. Taken together, these results indicate that IL-12 has potent immunomodulatory effects on allergic lung inflammation that depend on the timing of IL-12 administration relative to allergic sensitization and allergen challenge.
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PMID:Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses. 889 55

Crescentic glomerulonephritis (GN) demonstrates immunopathological features of a T helper (Th)1-directed delayed-type hypersensitivity (DTH) response. The capacity of Th2 cytokines to attenuate crescentic glomerular injury in this disease was examined by administering interleukin (IL)-4 and IL-10, singly and in combination. GN was induced by i.v. administration of sheep anti-mouse glomerular basement membrane (GBM) globulin to mice sensitized to sheep globulin 10 days earlier. Treatment (2.5 microg, i.p.) with IL-4, IL-10, or both IL-4 and IL-10 (IL-4 + 10), was started 1 h before sensitization and continued daily until the end of the study (10 days after administration of anti-GBM globulin). Control mice treated with PBS developed GN with glomerular accumulation of T cells and macrophages, crescents in 42.5 +/- 4.5 % of glomeruli (normal 0 %), proteinuria (8.3 +/- 0.9 mg/24 h, normal 0.74 +/- 0.08 mg/24 h, p <0.001) and renal impairment (creatinine clearance [cr/cl]: 93 +/- 12 microl/min, normal 193 +/- 10 microl/min, p < 0.001). Treatment with either IL-4, IL-10, or IL-4 + 10 prevented crescent formation (crescentic glomeruli: 0.8 +/- 0.5, 1.2 +/- 0.9, and 1.4 +/- 1.0 %, respectively, all p < 0.01 compared to control) and attenuated proteinuria (3.6 +/- 1.0, 2.2 +/- 0.5, and 2.9 +/- 0.5 mg/24 h, respectively, all p < 0.01 compared to control). IL-4 + 10 prevented development of renal impairment (cr/cl: 183 +/- 22 microl/min); IL-10 given alone limited the decline in renal function (cr/cl: 150 +/- 20 microl/min), but IL-4 alone did not provide any significant protection (cr/cl: 121 +/- 17 microl/min). All treatments markedly diminished glomerular T cell and macrophage accumulation, reduced interferon-gamma production by splenic T cells, prevented cutaneous DTH to the disease-initiating antigen and reduced antigen-specific immunoglobulin of the IgG2a and IgG3 isotypes. These data demonstrate that crescentic GN and renal impairment can be prevented by administration of Th2 cytokines and that this effect is associated with attenuation of the Th1 response to the disease-initiating antigen.
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PMID:Immune modulation with interleukin-4 and interleukin-10 prevents crescent formation and glomerular injury in experimental glomerulonephritis. 904 27

Because interleukin (IL)-10 is an immunoregulatory cytokine that is produced by keratinocytes exposed to UVB radiation (UVR), we determined whether IL-10 participates in either failed contact hypersensitivity (CH) induction or tolerance after acute, low-dose UVR. Murine recombinant IL-10 (200 ng) was injected intradermally on shaved abdominal skin. To assess the effects of IL-10 on CH induction, dinitrofluorobenzene (DNFB, 185 microg) was painted on the skin within 30 min after IL-10 was injected, and the mice were assayed 5 d later by ear challenge with dilute DNFB. To assess tolerance, DNFB (185 microg) was painted a second time on normal body-wall skin 14 d after DNFB was first painted on IL-10-injected skin; CH was then assayed on day 19. We found that mice that received DNFB on IL-10-injected skin developed CH comparable in intensity to that observed in PBS-injected controls. Thus, this dose of IL-10 did not prove to be deleterious to CH induction if hapten was painted on the injected site within 30 min. By contrast, mice that first experienced DNFB within 30 min, 1 d, or 3 d after IL-10 had been injected intracutaneously displayed hapten-specific tolerance. Moreover, intraperitoneally injected anti-IL-10 antibody prevented UVR- and cis-urocanic acid-dependent tolerance; anti-IL-10 antibody had no effect on TNF-alpha-induced tolerance and failed to restore CH induction after UVR exposures. These data indicate that IL-10 is an important mediator of the tolerance induced when hapten is painted on the skin of animals exposed to acute, low-dose UVR.
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PMID:Hapten-specific tolerance induced by acute, low-dose ultraviolet B radiation of skin is mediated via interleukin-10. 920 50

Using in situ hybridization with radiolabelled oligonucleotide probes, we studied the mRNA expression of IL-1beta, IL-4, IL-6, IL-10, IL-12, tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma (IFN-gamma), and transforming growth factor-beta (TGF-beta) in the brain during the lethal course of experimental meningitis in a rat model inoculated intracisternally with Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae and in uninfected control rats inoculated with the same volume of PBS. The production of IL-1beta, IL-4, IL-6 and IFN-gamma was also evaluated by immunohistochemistry. In the brain of Hib-inoculated rats, there was marked mRNA expression of IL-1beta, IL-6, TNF-alpha, IL-12 and IFN-gamma. IL-1beta, IL-6 and TNF-alpha were up-regulated throughout the observation period at 2, 8 and 18 h post-inoculation (p.i.), with similar patterns of induction. The Th1 cytokines IFN-gamma and TNF-beta were up-regulated within 8 h p.i. IL-10 and TGF-beta were down-regulated at 18 h p.i., while IL-4 was not detected. In contrast, the brain of S. pneumoniae-inoculated rats showed lower levels of IL-1beta, IL-6 and TNF-alpha, but higher levels of TNF-beta and detectable mRNA expression of IL-4 when compared with Hib-inoculated rats. IL-12, IFN-gamma, IL-10 and TGF-beta exhibited similar patterns of induction in the brains of Hib- and S. pneumoniae-inoculated rats. At 18 h p.i., immunohistochemistry showed similar patterns of IL-1beta, IL-4, IL-6 and IFN-gamma as mRNA expression in the brains of Hib- and S. pneumoniae-inoculated rats. The differences of cytokine profiles induced by the two bacterial strains may imply that different immunomodulating approaches should be considered, depending on etiology.
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PMID:Haemophilus influenzae and Streptococcus pneumoniae induce different intracerebral mRNA cytokine patterns during the course of experimental bacterial meningitis. 927 17

The regulatory functions of IL-12 on granuloma formation by the eggs of S. japonicum in the lungs of BALB/c mice were studied. Mice were injected i.v. with the eggs to induce the pulmonary granuloma. On days 0, 1, 2, 3, 7, 8 after injection, mice were injected i.p. with murine rIL-12 at a dose of 1 microgram day-1 (Group I) or 3 micrograms day-1 (Group II) or with PBS as a control (Group III). On day 10, all mice were sacrificed. The areas of pulmonary granulomas in histological sections were quantitatively measured by image analyser and the levels of mRNA for IL-10, IFN-gamma, IL-12 and IL-5 were assayed by reverse transcriptase PCR (RT-PCR). The results showed that the mean area per granuloma was significantly decreased in Groups I and II as compared with Group III. As for cytokine induction, IL-10- and IFN-gamma-specific bands appeared in Groups I and II, but not in Group III. Bands for IL-5 appeared in all groups, while bands for IL-12 were not detected in any group. It is suggested that IL-12 could inhibit the Th2 dominant granuloma formation induced by the eggs of S. japonicum.
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PMID:Effect of IL-12 on granuloma formation induced by injected Schistosoma japonicum eggs. 927 91

It has recently been found that in systemic lupus erythematosus (SLE), a multisystem inflammatory disorder characterized by autoantibody production and decreased cellular immune response, increased spontaneous production of IL-10 occurs. The immunomodulator AS101 (ammonium trichloro(dioxoethylene-0,0')tellurate) was previously shown to significantly decrease IL-10 levels in cancer patients and in murine models. This study shows that AS101 inhibits the development of SLE-related autoimmune pathological manifestations. AS101 decreased the spontaneous IL-10 production by mononuclear cells from SLE patients in vitro. In vivo, systemic injection of AS101 to SCID mice transplanted with mononuclear cells from SLE patients significantly decreased serum human IL-10 levels. There was also a decrease in all serum human Ig isotypes, in anti-dsDNA, and in anti-Sm Igs. In the New Zealand Black/New Zealand White/F1 model, AS101 significantly increased serum TNF-alpha and IFN-gamma while decreasing IL-10 levels; these changes were accompanied by a rapid decrease in anti-dsDNA and anti-ssDNA Igs. More importantly, continuous treatment of New Zealand Black/New Zealand White/F1 mice with AS101 for 6 mo led to the development of proteinuria in 30% of the treated mice compared with 100% in PBS-treated mice (p < 0.001). AS101 treatment reduced the level of immmune complex deposition in the glomeruli, prevented glomerular hypercellularity and mesangial expansion and led to a much smaller mean glomerular volume in treated mice (185 +/- 6 vs 428 +/- 47.103 microm3; p < 0.01). We suggest that treatment with a nontoxic immunomodulator such as AS101, previously used in phase II trials on cancer patients, may be an effective therapeutic approach for controlling SLE.
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PMID:Delay in the onset of systemic lupus erythematosus following treatment with the immunomodulator AS101: association with IL-10 inhibition and increase in TNF-alpha levels. 930 Jun 85

Nasal administration of microg doses of acetylcholine receptor (AChR) is effective in preventing the development of B cell-mediated EAMG in the Lewis rat, a model for human MG. In order to investigate whether nasal administration of AChR modulates ongoing EAMG, Lewis rats were treated nasally with AChR 2 weeks after immunization with AChR and Freund's complete adjuvant. Ten-fold higher amounts of AChR given nasally (600 microg/rat) were required to ameliorate the manifestations of EAMG compared with the amounts necessary for prevention of EAMG. In lymph node cells from rats receiving 600 microg/rat of AChR, AChR-induced proliferation and interferon-gamma (IFN-gamma) secretion were reduced compared with control EAMG rats receiving PBS only. The anti-AChR antibodies in rats treated nasally with 600 microg/rat of AChR had lower affinity, reduced proportion of IgG2b and reduced capacity to induce AChR degradation. Numbers of AChR-reactive IFN-gamma and tumour necrosis factor-alpha (TNF-alpha) mRNA-expressing lymph node cells from rats treated nasally with 600 microg/rat of AChR were suppressed, while IL-4, IL-10 and transforming growth factor-beta (TGF-beta) mRNA-expressing cells were not affected. Collectively, these data indicate that nasal administration of AChR in ongoing EAMG induced selective suppression of Th1 functions, i.e. IFN-gamma and IgG2b production, but no influence on Th2 cell functions. The impaired Th1 functions may result in the production of less myasthenic anti-AChR antibodies and contribute to the amelioration of EAMG severity in rats treated with AChR 600 microg/rat by the nasal route.
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PMID:Nasal tolerance in experimental autoimmune myasthenia gravis (EAMG): induction of protective tolerance in primed animals. 952 90


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