Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary oral antigen exposure normally induces mucosal immunity and an active suppression of the systemic immune response. Patients with systemic lupus erythematosus (SLE) have increased antibodies to bovine gamma-globulin (BGG), which suggested a possible failure of oral tolerance in SLE. We examined this possibility in murine lupus. NZB/W females were fed BGG or saline and were subsequently immunized ip. Primary and secondary responses were assessed. At 1 month of age the mice tolerized normally in response to feeding with BGG but, at 4 months of age, not only did they not tolerize, the mice fed BGG had a 5- to 7-fold higher response to parenteral immunization than did the saline-fed mice. Control strain mice tolerized normally at both ages (a 5- to 10-fold lower response). Conversely, when fed ovalbumin, NZB/W females tolerized normally at both 1 and 4 months of age, and patients with SLE had normal levels of antibody to this antigen. However, we also found increased levels of antibodies to bovine casein in SLE patients, and found that NZB/W mice failed to orally tolerize with this antigen at either 1 or 4 months of age. Thus, the failure of oral tolerance in the NZB/W mice appears to be antigen specific and age dependent and, at least with respect to these three antigens, appears to parallel the antibody patterns seen in human SLE.
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PMID:Failure of oral tolerance in (NZB X NZW)F1 mice is antigen specific and appears to parallel antibody patterns in human systemic lupus erythematosus (SLE). 295 Oct 41

The role of nutrition in modulating autoantibody expression in murine lupus has become well documented. One such nutritional factor, zinc deficiency, has received significant attention because of the well-known effects of zinc on the immune function of genetically normal animals. Moreover zinc-deficient diets retard autoantibody production in NZB, NZB/W, and MRL/1 mice; such deprivation also enhances survival in all three strains. Because zinc nutriture influences vitamin A metabolism, it has been postulated that the immunologic effects of zinc deficiency are mediated in part by the reduction of vitamin A levels seen in zinc deprivation. To explore this possibility we studied the influence of vitamin A deficiency, in zinc well-nourished mice, on autoantibody production in NZB mice. Groups of NZB mice, beginning at 6 mo of age, were fed a vitamin A-deficient diet or a control diet ad libitum or pair-fed to the deficient group. The diet contained casein as the protein source and contained adequate levels of trace elements and vitamins. Despite our hypothesis that the reduction of autoantibodies in zinc-deficient NZB mice might be mediated by secondary vitamin A deficiency, we found that vitamin A-deficient animals manifested more severe hypergammaglobulinemia and an earlier onset of both NTA and IgM anti-erythrocyte autoantibodies than did vitamin A-sufficient mice. These results illustrate the importance of rigorous studies of select nutritional parameters and warn of the possibility of clinical harm in feeding inappropriate diets to patients with systemic lupus erythematosis.
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PMID:Nutritional factors and autoimmunity. IV. Dietary vitamin A deprivation induces a selective increase in IgM autoantibodies and hypergammaglobulinemia in New Zealand Black mice. 660 78

The acute-phase plasma protein response to disease activity in murine models of autoimmune lupus-like disease was investigated by measurement of the concentration of serum amyloid P component (SAP) in NZB X W and MRL/l mice. The levels of SAP, which is a major acute-phase protein in mice, did not rise at all in response to progression of disease in NZB X W mice between the ages of 1 and 9 mo. This resembles the behavior of acute-phase proteins such as C-reactive protein and serum amyloid A protein in human systemic lupus erythematosus, and just as in human lupus, where the occurrence of intercurrent microbial infection can stimulate an acute-phase response, so injection of bacterial lipopolysaccharide or casein into the NZB X W mice stimulated "normal" acute-phase SAP production. In marked contrast, MRL/l mice developed greatly increased levels of SAP, which correlated closely with progression of their pathology as they aged. The disease profile of the MRL/l strain includes rheumatoid factors and spontaneous polyarthritis and their SAP response resembles the behavior of acute phase proteins in human rheumatoid arthritis. Different patterns of acute-phase response in different autoimmune disorders may thus be a reflection of the genetic predisposition to particular diseases and/or contribute to their pathogenesis. The existence of animal counterparts for the various clinical patterns of human acute-phase protein production will assist in experimental investigation of the underlying mechanisms and of the biological role of the acute-phase response.
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PMID:The acute-phase response in (NZB X NZW)F1 and MRL/l MICE. 715 12

Isoflavones, which are phytoestrogens present in large quantities in soy and soy-derived products, have estrogenic activity, inhibit protein tyrosine kinase, and exert other effects in the human body. Thus, the recent spread of soy consumption in Western populations emphasizes the need to more fully understand the potential effects in the body, especially in abnormal immune conditions. In the present study, the influence of a soy diet on lupus disease in MRL/Mp-lpr/lpr (MRL/lpr) mice was investigated. Weanling female MRL/lpr mice (4 weeks) were fed a soy diet (20% soybean protein and 5% soybean oil). The soy diet exacerbated renal damage; findings in this mouse strain included accelerated proteinuria, elevated serum creatinine concentrations, and reduced creatinine clearance. No effects were detected, however, in C3H/HeN mice, which have the same H-2(k) genetic background as MRL/lpr mice do. A tendency toward an increase in thymus weight and proliferation of T cells in spleen and B cells in lymph nodes were found at the age of 16 weeks. These findings indicate that a soy diet, in comparison with a casein diet, significantly exacerbates the clinical course of this autoimmune disease. Further research on the mechanism of this effect of soy-rich diets is needed, and isoflavone supplementation for systemic lupus erythematosus patients should be carefully reevaluated.
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PMID:A soy diet accelerates renal damage in autoimmune MRL/Mp-lpr/lpr mice. 1603 50

GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is a key enzyme of the glycolytic pathway and it is related to the occurrence of some diseases. The cDNA and the genomic sequence of GAPDH were cloned successfully from the Giant Panda (Ailuropoda melanoleuca) using the RT-PCR technology and Touchdown-PCR, respectively. Both sequences were analyzed preliminarily. The cDNA of GAPDH cloned from the Giant Panda is 1191 bp in size, contains an open reading frame of 1002 bp encoding 333 amino acids. The genomic sequence is 3941 bp in length and was found to possess 10 exons and 9 introns. Alignment analysis indicates that the nucleotide sequence and the deduced amino acid sequence are highly conserved in some mammalian species, including Homo sapiens, Mu musculus, Rattus norvegicus, Canis lupus familiaris and Bos taurus. The homologies for the nucleotide sequences of the Giant Panda GAPDH to that of these species are 90.67, 90.92, 90.62, 95.01 and 92.32% respectively, while the homologies for the amino acid sequences are 94.93, 95.5, 95.8, 98.8 and 97.0%. Primary structure analysis revealed that the molecular weight of the putative GAPDH protein is 35.7899 kDa with a theoretical pI of 8.21. Topology prediction showed that there is one Glyceraldehyde 3-phosphate dehydrogenase active site, two N-glycosylation sites, four Casein kinase II phosphorylation sites, seven Protein kinase C phosphorylation sites and eight N-myristoylation sites in the GAPDH protein of the Giant Panda. The GAPDH gene was overexpressed in E. coli BL21. The results indicated that the fusion of GAPDH with the N-terminally His-tagged form gave rise to the accumulation of an expected 43 kDa polypeptide. The SDS-PAGE analysis also showed that the recombinant GAPDH was soluble and thus could be used for further functional studies.
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PMID:cDNA, genomic sequence cloning and overexpression of glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) from the Giant Panda. 2058 83

The course and severity of lupus in spontaneous murine lupus models varies among laboratories, which may be due to variations in diet, housing and/or local environmental conditions. In this study, we investigated the influence of common rodent diets while keeping other factors constant. Female lupus-prone MRL/lpr (MRL/MpJ-Faslpr/J) mice were subjected to the same housing conditions and given one of the three diets: Teklad 7013 containing isoflavone-rich soy and alfalfa, Harlan 2018 isoflavone-rich soy-based diet or Research Diets Inc. D11112226 (RD) purified-ingredients diet containing casein and no phytoestrogens. While the total caloric intake was similar among all three treatment groups, mice fed on the 2018 diet developed higher levels of proteinuria and mice fed on either 7013 or 2018 developed higher levels of glomerular immune complex deposition. Remarkably, mice fed the RD diet had markedly decreased proteinuria with diminished C3, total IgG, IgG1 and IgG3 immune complex deposition, along with reduced CD11b+ cellular infiltration into the glomeruli. The type of diet intake also influenced cytokine production, fecal microbiota (increased Lachnospiraceae in mice fed on 2018), altered microRNAs (miRNAs; higher levels of lupus-associated miR-148a and miR-183 in mice fed on 7013 and/or 2018) and altered DNA methylation. This is the first study to comprehensively compare the cellular, molecular and epigenetic effects of these commercial diets in murine lupus.
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PMID:Commercial rodent diets differentially regulate autoimmune glomerulonephritis, epigenetics and microbiota in MRL/lpr mice. 2863