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- Roeske-Nielsen, A., et al.
(författare)
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Sulfatide inhibits fibroblast growth, activation and oxidative stress induced by ectopic insulin
- 2023
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Ingår i: Diabetes Obesity & Metabolism. - 1462-8902.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the effect of sulfatide on gene expression and proliferation of human primary fibroblasts induced by insulin, insulin-like growth factor-1 and human growth hormone. Materials and Methods: Human primary fibroblasts were exposed to 1, 3 and 30 mu M of sulfatide or its precursor galactosylceramide (GalCer). Proliferation was determined by 3H-thymidine incorporation and gene expression via microarray analysis. Results: Sulfatide and GalCer reduced the growth rate of fibroblasts by 32%-82% when exposed to 0.5 nM insulin. After challenge with 120 mu M of H2O2, sulfatide reduced membrane leakage. Fibroblast gene expression was altered by sulfatide in gene pathways associated with cell cycle/growth, transforming growth factor-beta function, and encoding of proteins involved in intracellular signalling. NFKBIA, a key control element in NF-kappa B regulation, was decreased 2-fold by sulfatide. Conclusions: Sulfatide strongly inhibits fibroblast growth. We therefore suggest the addition of sulfatide to injectable commercial insulin formulations, which would reduce adverse fibroblast growth and improve well-being in patients with diabetes.
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| 3. |
- Roeske-Nielsen, A., et al.
(författare)
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Beta-galactosylceramide increases and sulfatide decreases cytokine and chemokine production in whole blood cells
- 2004
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Ingår i: Immunol Lett. - : Elsevier BV. - 0165-2478. ; 91:2-3, s. 205-11
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Tidskriftsartikel (refereegranskat)abstract
- The glycosphingolipid sulfatide and its immediate precursor beta-galactosylceramide (GalCer) are present in the pancreatic beta-cell in equimolar concentrations and may play a role in islet pathology. Previous studies of mononuclear cells have shown that sulfatide tends to decrease and GalCer tends to increase the production of proinflammatory cytokines. In this study we investigated the influence of various isoforms of sulfatide on the production of cyto- and chemokines and tested whether the opposing effects of GalCer and sulfatide could counter one another in competition assays. PHA-, LPS-, or unstimulated whole blood cultures were incubated with 30 microg/ml of native sulfatide (isolated from pig brains), C:16:0 and C:24:0 analogues of sulfatide, or native GalCer preparations. After 24 h, the supernatant levels of proinflammatory cytokines and chemokines were quantitated by ELISA. The general trend was for the sulfatides to lower the production of the cytokines, and for GalCer to increase it. In competition assays, native sulfatide dampened the stimulatory effects of GalCer but did not abolish cytokine release; GalCer, on the other hand, nullified the effect of native sulfatide at a ratio of four sulfatide molecules to one GalCer molecule. C:16:0 sulfatide appeared to have a stronger effect than C:24:0 sulfatide. The C:16:0 analogue decreased IL-1beta, IL-6, TNF-alpha, MIP-1alpha and IL-8 to 3-56% of control values (P < 0.05-0.01), while GalCer increased their production 2- to 10-fold (P < 0.01). In conclusion, sulfatide decreases the in vitro production of proinflammatory cytokines, whereas GalCer has the opposite effect.
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- Nicoletti, F, et al.
(författare)
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Early prophylaxis with recombinant human interleukin-11 prevents spontaneous diabetes in NOD mice
- 1999
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 48:12, s. 2333-2339
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the effects of recombinant human (rh) interleukin (IL)-11 on the development of spontaneous and cyclophosphamide-induced diabetes in female NOD mice. Prolonged treatment with rhIL-11 10 microg i.p. five consecutive times a week between the 4th and 22nd weeks of age significantly suppressed both development and cumulative incidence of type 1 diabetes. Disease protection was transient because most of the animals developed type 1 diabetes within 3 months of treatment withdrawal. In contrast, rhIL-11 failed to prevent type 1 diabetes when administered for the first time to euglycemic 18-week-old NOD mice. Most likely, this discrepancy was not due to age-dependent differences in the immunological responses of NOD mice to rhIL-11 because staphylococcus aureus enterotoxin B-induced tumor necrosis factor (TNF) and IL-12 production were equally suppressed by rhIL-11 in 12- and 25-week-old NOD mice. Relative to controls, NOD mice pretreated with rhIL-11 also showed significantly diminished blood levels of TNF, interferon-gamma, and IL-12 induced by anti-CD3 antibody and/or lipopolysaccharide. The results demonstrate that rhIL-11 has powerful anti-inflammatory effects that are capable of down-regulating early immunodiabetogenic pathways in NOD mice.
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- Svenson, M., et al.
(författare)
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Monitoring patients treated with anti-TNF- biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies
- 2007
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 46:12, s. 1828-1834
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Infliximab is an anti-tumour necrosis factor-alpha (TNF-alpha) mousehuman IgG1/k antibody used to treat patients with rheumatoid arthritis (RA) and other inflammatory diseases. Unfortunately, response failure and side-effects due to immunogenicity of the drug are not rare. In this study, we have compared different methods of assessing drug levels and anti-infliximab antibodies (Abs) and analysed the character of these Abs in sera of RA patients treated with infliximab for 1.5-18 months. Methods. Functional serum infliximab levels and anti-infliximab Abs were measured by fluid-phase RIAs using I-125-labelled ligands in combination with molecular size and affinity chromatography, and immune complex precipitation. Results. Anti-infliximab Abs were predominantly IgG, 36% being IgG4, and half the immune complexes were lambda-light-chain-positive. Ab titres were associated with inhibition of TNF binding to the drug, and low trough levels of infliximab were most frequent in anti-infliximab Ab-positive sera. Cross-binding to two other anti-TNF drugs was not observed. Detection of anti-infliximab Abs by solid-phase RIA using cross-binding of plastic-fixed and soluble infliximab exhibited low sensitivity and the data were inconsistent with results obtained from binding of the Abs to soluble infliximab. Conclusions. Specific and neutralizing anti-infliximab antibodies develop in RA patients treated with infliximab, and that low trough levels of functional infliximab are associated with the presence of such antibodies. The most sensitive antibody assay involved binding to soluble and intact infliximab. Assessments of bioavailability and immunogenicity of anti-TNF biologicals may be used to optimize dose regimens and prevent prolonged use of inadequate therapy.
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