Home About us Contact
|
Home About us Contact | ||
|
|
||
Tolerogenic Peptide (tolerogenic + peptide)
Selected AbstractsA tolerogenic peptide down-regulates mature B cells in bone marrow of lupus-afflicted mice by inhibition of interleukin-7, leading to apoptosisIMMUNOLOGY, Issue 2 2009Hava Ben-David Summary Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by T and B cells. It is characterized by a variety of autoantibodies and systemic clinical manifestations. A tolerogenic peptide, designated hCDR1, ameliorated the serological and clinical manifestations of SLE in both spontaneous and induced models of lupus. In the present study, we evaluated the status of mature B cells in the bone marrow (BM) of SLE-afflicted mice, and determined the effect of treatment with the tolerogenic peptide hCDR1 on these cells. We demonstrate herein that mature B cells of the BM of SLE-afflicted (New Zealand Black × New Zealand White)F1 mice were largely expanded, and that treatment with hCDR1 down-regulated this population. Moreover, treatment with hCDR1 inhibited the expression of the pathogenic cytokines [interferon-, and interleukin (IL)-10], whereas it up-regulated the expression of transforming growth factor-, in the BM. Treatment with hCDR1 up-regulated the rates of apoptosis of mature B cells. The latter was associated with inhibited expression of the survival Bcl-xL gene and of IL-7 by BM cells. Furthermore, the addition of recombinant IL-7 abrogated the suppressive effects of hCDR1 on Bcl-xL in the BM cells and resulted in elevated levels of apoptosis. Hence, the down-regulated production of IL-7 contributes to the hCDR1-mediated apoptosis of mature B cells in the BM of SLE-afflicted mice. [source] Suppression of immune responses to ,-lactoglobulin in mice by the oral administration of peptides representing dominant T cell epitopesJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 3 2008Koko Mizumachi Abstract BACKGROUND: The significance of oral tolerance in the treatment of adverse immune reactions such as allergic and autoimmune diseases has been noted. In the present study, peptides that could effectively induce oral tolerance to bovine ,-lactoglobulin (BLG), a milk allergen, were investigated in a murine model. RESULTS: The oral administration of peptides corresponding to the T cell epitope regions of BLG, i.e. p42,56, p62,76 and p139,154, apparently down-regulated T cell proliferation to BLG. The in vitro cytokine production by the lymph node cells from the peptide-fed mice cultured in the presence of the antigen was also analysed. It was found that p62,76 and p139,154 feeding suppressed the production of both Th1 and Th2 types. Interestingly, p139,154 feeding suppressed both T cell and antibody responses to BLG. Additionally, p139,154 feeding diminished BLG-specific IgE and IgG1 antibody responses. CONCLUSION: The unique tolerogen peptide p139,154 that could suppress both T and B cell responses to BLG in a murine model was identified. These findings can be useful for the selection of an optimum tolerogenic peptide to prevent and treat milk and other food allergies. Copyright © 2007 Society of Chemical Industry [source] Amelioration of brain pathology and behavioral dysfunction in mice with lupus following treatment with a tolerogenic peptideARTHRITIS & RHEUMATISM, Issue 12 2009Smadar Lapter Objective Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is manifested by neurologic deficits and psychiatric disorders. The aim of this study was to examine SLE-associated CNS pathology in lupus-prone (NZB × NZW)F1 (NZB/NZW) mice, and to evaluate the ameliorating effects of treatment with a tolerogenic peptide, hCDR1 (human first complementarity-determining region), on these manifestations. Methods Histopathologic analyses of brains from lupus-prone NZB/NZW mice treated with vehicle, hCDR1, or a control scrambled peptide were performed. The messenger RNA expression of SLE-associated cytokines and apoptosis-related molecules from the hippocampi was determined. Anxiety-like behavior was assessed by open-field tests and dark/light transfer tests, and memory deficit was assessed using a novel object recognition test. Results Infiltration was evident in the hippocampi of the lupus-afflicted mice, and the presence of CD3+ T cells as well as IgG and complement C3 complex deposition was observed. Furthermore, elevated levels of gliosis and loss of neuronal nuclei immunoreactivity were also observed in the hippocampi of the mice with lupus. Treatment with hCDR1 ameliorated the histopathologic changes. Treatment with hCDR1 down-regulated the high expression of interleukin-1, (IL-1,), IL-6, IL-10, interferon-,, transforming growth factor ,, and the proapoptotic molecule caspase 8 in the hippocampi of the mice with lupus, and up-regulated expression of the antiapoptotic bcl -xL gene. Diseased mice exhibited increased anxiety-like behavior and memory deficit. Treatment with hCDR1 improved these parameters, as assessed by behavior tests. Conclusion Treatment with hCDR1 ameliorated CNS pathology and improved the tested cognitive and mood-related behavior of the mice with lupus. Thus, hCDR1 is a novel candidate for the treatment of CNS lupus. [source] | ||||||||||