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)

The expression of the complement protein C3 in extrahepatic tissues is highly regulated during the course of inflammation. Hence, systemic acute phase stimuli such as bacterial lipopolysaccharide (LPS) and autoimmune nephritis in aged 'lupus mice' (MRL-lpr/lpr and NZB x NZW F1) both lead to increased C3 mRNA expression in whole kidney. In situ hybridization was used to determine the intrarenal cell type(s) capable of constitutive and regulated C3 mRNA expression. Normal mice injected with Escherichia coli LPS show a marked increase in whole kidney C3 mRNA over control (saline-injected) animals. The renal C3 mRNA in LPS-stimulated mice was found in cortical tubular epithelium. By contrast, in aged (18 week) MRL-lpr/lpr mice, which develop lupus nephritis, the increased intrarenal C3 messenger RNA was localized to perivascular inflammatory cells surrounding medium-sized arteries. Similar perivascular infiltrates were seen in the lungs of the MRL-lpr/lpr mice, and focal inflammatory cell infiltrates were also found in the myocardium. Leucocytes in these infiltrates accounted for the increased C3 expression in these tissues. These findings suggest cell as well as tissue specificity of the response to inflammatory stimuli in the local extrahepatic production of the third component of complement.
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PMID:Cellular specificity of murine renal C3 expression in two models of inflammation. 803 15

We previously purified a 55 kDa protein that preferentially expands anti-DNA antibody production both in vitro and in vivo across the H-2 barrier from culture supernatants of KML1-7 cells, cloned from a lupus-prone MRL/lpr mouse. By using the purified protein, termed nucleobindin (Nuc), we cloned cDNA and produced recombinant(r) Nuc in Escherichia coli. To elucidate the function of rNuc in vivo, we initially injected intraperitoneally 5 micrograms of rNuc without adjuvant into female MRL/n mice at 8 weeks of age and continued injection twice a week. As early as 5 weeks after administration, all mice treated showed an increase in IgG anti-double stranded (ds) DNA antibodies accompanied by IgG hypergammaglobulinemia (HG). Of particular interest was that these mice also produced anti-U1RNP antibodies and rheumatoid factor (RF) of IgG class, but not anti-Sm antibodies. Histopathologically, hypercellularity with occasional crescents in the glomeruli was observed, but evidence for lupus nephritis was lacking, indicating that some factors other than Nuc are necessary for the development of a lupus syndrome observed in MRL/lpr mice. Similar administration of lipopolysaccharide into MRL/n mice failed to induce autoantibodies except for a slight increase in serum IgG, suggesting that these autoimmune responses are not due simply to polyclonal B-cell activation. The presence of rNuc will give us a clue for further understanding of autoimmunity.
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PMID:Novel autoimmune phenomena induced in vivo by a new DNA binding protein Nuc: a study on MRL/n mice. 814 93

Previous studies in our laboratory demonstrated an altered immuno-endocrine feedback communication via the hypothalamo-pituitary-adrenal (HPA) axis, which may be an important modulatory factor in the development of spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. These birds show a significantly lower, or even absent, increase in serum glucocorticoid levels in response to an intravenous injection of antigen or conditioned medium (CM) from mitogen-stimulated spleen cells known to contain glucocorticoid-increasing factors (GIFs), notably interleukin-1 (IL-1). The present study was aimed at investigating this feedback regulation in animal models with spontaneous systemic autoimmune diseases, such as the UCD-200 chicken, which serves as a model for human scleroderma, and various murine lupus models. In contrast to OS chickens, UCD-200 chickens displayed a nearly normal plasma corticosterone surge in response to CM, and IL-1 was again identified as the primary GIF in CM. Recombinant IL-1 also induced a drastic increase in plasma corticosterone levels in various strains of normal mice. A similar increase was observed in the bacterial lipopolysaccharide-resistant C3H/HeJ strain, thus excluding the possibility of bacterial endotoxin contamination. However, in young lupus-prone (NZB/W)F1 and MRL/MP-lpr mice, a significantly lower increase in plasma corticosterone levels was observed after injection of recombinant IL-1, suggesting a deficient immuno-endocrine communication via the HPA loop in this instance as well. Detailed studies to identify further cytokines with GIF activity in the avian and murine systems showed that both IL-6 and tumor necrosis factor-alpha could induce increased plasma corticosterone levels in mice, but not in chickens. IL-3, IL-8, transforming growth factor-beta, interferon-gamma and granulocyte-macrophage colony-stimulating factor were devoid of GIF activity in both chickens and mice.
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PMID:Disturbed immuno-endocrine communication via the hypothalamo-pituitary-adrenal axis in autoimmune disease. 821 76

Systemic lupus erythematosus is characterized by profound changes of the immune system. We report on alterations of the macrophage system in the murine NZB/W model of this disease. A greatly increased number of mature macrophages was isolated from the liver of NZB/W mice as compared to BALB/c mice and several other inbred strains used as healthy controls. In addition, the macrophage precursor compartment in the liver of NZB/W mice was expanded severalfold as measured by proliferation of light-fraction nonadherent nonparenchymal cells (NPCs) in response to colony-stimulating factors. Functional properties of the macrophages isolated from various anatomic sites of the lupus-prone mice were tested. Production of monokines by macrophages from liver, spleen, and peritoneal cavity, calculated on a per cell basis, was in the same range as in several healthy control strains tested. Yet the overall production of these immunoregulatory molecules by the increased liver macrophage system, the body's largest compartment of macrophages, is likely to result in increased levels of circulating monokines in the plasma of lupus-prone NZB/W mice. Indeed, significantly elevated levels of interleukin-6, interleukin-1, and colony-stimulating activity could be demonstrated in the plasma of these mice both spontaneously and after stimulation with lipopolysaccharide. A possible contribution of the expansion of the macrophage system to the development of the disease is discussed.
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PMID:Expansion of the liver-associated macrophage system in systemic lupus erythematosus-prone NZB/W mice. 845 53

The mechanism, or mechanisms, responsible for enhancement of renal disease after episodes of infection are poorly understood. We used the BXSB mouse as a lupus model of autoimmune disease and we used bacterial lipopolysaccharide (LPS) as a surrogate infectious agent to gain some insight into the mechanism by which infections promote enhancement of autoimmune disease to chronicity. BXSB mice were exposed to LPS for 5 weeks, LPS was withdrawn and various tests and measurements were performed 6 weeks thereafter. Matched BXSB mice exposed to vehicle injections for 5 weeks served as controls. We verified that previous exposure to LPS enhances polyclonal B cell activation, impairs carrier function of blood cells for immune complexes, increases deposition of immune complexes in the microcirculation and promotes glomerular inflammation and sclerosis. These changes occurred at 6 weeks after withdrawal of LPS in the presence of unimpaired function of mononuclear phagocytes. Some of the effects of LPS are reversible, others are partially so and others are irreversible. Altered immune functions elicited by prior exposure to LPS can result in enhanced involvement of various renal compartments and can result in renal insufficiency.
Lupus 1995 Oct
PMID:Enhancement of renal disease in BXSB lupus prone mice after prior exposure to bacterial lipopolysaccharide. 856 25

Systemic lupus erythematosus is characterized by polyclonal B cell activation, the production of autoantibodies, and often by renal disease. Previous studies demonstrated that unfractionated B cells from several strains of mice with lupus hyperproliferate in culture when stimulated with lipopolysaccharide (LPS) or anti-IgM. We wished to further examine proliferation of resting B cells from the BXSB mouse model of lupus and mice with the Yaa allele, when activated with a number of stimuli. Our work demonstrates that: (1) resting B cells from mice containing the Yaa allele hyperproliferated compared to that seen with B cells from mice lacking the Yaa allele, (2) this hyperproliferation occurred whether cells were stimulated with phorbol myristate acetate/ionomycin, LPS, anti-IgM, or CD40L cross-linking, (3) this hyperproliferation is specific to B and not T cells. Taken together these data suggest that one mechanism by which the Yaa allele contributes to the accelerated onset of lupus in BXSB male mice is through its influence on B cell activation.
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PMID:Hyperproliferation of BXSB B cells is linked to the Yaa allele. 890 45

Polyclonal B cell activation has been thought to play the critical role in production of autoantibodies, and possible activation of autoreactive T cells in murine lupus, especially abnormal expansion of CD5+ B cells, is one of the characteristic findings in these mice. The aim of this study was to investigate further the characteristics and function of CD5+ and CD5- B cells. Both CD5+ and CD5- B cells were isolated for in vitro autoantibody production, cytokine expression and in vivo anti-DNA antibody production with reconstitution of severe combined immunodeficient (SCID) mice. The data showed: (i) both CD5+ and CD5- B cells produced a high level of anti-DNA antibody after stimulation with lipopolysaccharide (LPS) plus IL-5; (ii) both peritoneal CD5+ and CD5- B cells expressed a high level of IL-10 mRNA after stimulation with LPS, while in contrast CD5- B cells of non-autoimmune BALB/c mice did not express IL-10 mRNA after stimulation; (iii) SCID mice reconstituted with either CD5+ or CD5- B cells all produced significant levels of anti-DNA antibodies in vivo and manifested with proteinuria. These data suggest both CD5+ and CD5- B cells play important roles in polyclonal B cell activation and subsequent autoantibody production. Generalized polyclonal B cell activation, instead of expanding a certain subpopulation of B cells, contributed to the pathogenesis of autoimmunity in murine lupus.
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PMID:In vitro and in vivo functional analysis of CD5+ and CD5- B cells of autoimmune NZB x NZW F1 mice. 891 70

Protease nexin 1 (PN-1), a potent serpin-class antiprotease, is thought to be synthesized in the murine kidney. However, neither the cellular localization of PN-1 synthesis nor its role has yet been defined. To address these questions, we determined by in situ hybridizations RNase protection assay and immunoblotting, the sites of PN-1 mRNA accumulation in normal mouse kidneys and the modulation of PN-1 expression in several pathological conditions. In normal kidneys, PN-1 mRNA was detected primarily in glomeruli, most likely in mesangial cells. The glomerular expression of PN-1 was substantially enhanced not only in lupus-like glomerulonephritis (induced by IgG3 monoclonal rheumatoid factors or occurring spontaneously in lupus-prone mice), but also in mild glomerular lesions associated with intracapillary thrombi induced by IgG3 anti-trinitrophenyl monoclonal antibodies. In contrast, no modulation of PN-1 mRNA levels was observed during the course of lipopolysaccharide-induced acute tubular necrosis. A constitutive PN-1 gene expression and its up-regulation during glomerular injury suggest a possible role for PN-1 in glomerular biology. In view of its high inhibitory activity towards thrombin, mesangial PN-1 may be involved in the control of glomerular coagulation following initial glomerular injuries.
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PMID:Protease nexin 1 in the murine kidney: glomerular localization and up-regulation in glomerulopathies. 894 77

It still remains unclear how anti-phospholipid antibody develops in a specific patient group, however, it is possible that certain microorganism(s) may cause anti-cardiolipin antibody (aCL) development since aCL is frequently detected in patients with Treponema pallidum (TP) and/or other infectious diseases. Accordingly, we conducted an investigation to clarify whether or not anticardiolipin antibody (aCL) and/or lupus anticoagulant (LA) can be induced in rabbits by immunization with Gram-positive or -negative microorganism derivatives, such as lipoteichoic acid, lipopolysaccharide and lipid A. We detected the induction of SLE type-aCL (beta 2GPI-dependent) and LA in some rabbits immunized with lipid A and lipoteichoic acid, thereby suggesting that some microorganisms may contribute to even the production of pathogenic (SLE-type) antiphospholipid antibody.
Lupus 1996 Dec
PMID:Induction of anticardiolipin antibody and/or lupus anticoagulant in rabbits by immunization with lipoteichoic acid, lipopolysaccharide and lipid A. 911 2

Interleukin 4 (IL-4) is a cytokine that regulates growth and differentiation of lymphoid and nonlymphoid cells. To study the molecular basis of IL-4 function, we used a cDNA subtraction approach based on the representational difference analysis method. This subtractive amplification technique allowed us to use small amounts of RNA from lipopolysaccharide +/- IL-4-stimulated normal B cells to obtain IL-4-induced genes from these cells. We report here on one such gene, Fig1 (interleukin-four induced gene 1), the first characterized immediate-early IL-4 inducible gene from B cells. Fig1 expression is strikingly limited to the lymphoid compartment. B cells, but not T cells or mast cells, express Fig1 in response to IL-4 within 2 hr in a cycloheximide resistant manner. IL-2, IL-5, and I1-6 do not induce Fig1 in culture. Fig1 maps between Klk1 and Ldh3 on mouse chromosome 7, near two loci involved with murine lupus, Sle3 and Lbw5. The Fig1 cDNA sequence encodes a predicted 70-kDa flavoprotein with best homology to the monoamine oxidases, particularly in domains responsible for FAD binding.
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PMID:Fig1, an interleukin 4-induced mouse B cell gene isolated by cDNA representational difference analysis. 912 25


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