Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the influence of different saturations of dietary fat on autoantibody production and disease courses, autoimmune NZB/NZW F1 (NZB/W F1) mice were fed diets containing 20% palm oil, lard/soybean oil, soybean oil, canola oil or fish oil at 5 months of age. Sera levels of anti-DNA antibodies, proteinuria and life span were followed regularly. In addition, peritoneal resident cells were isolated and mediators such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E2 (PGE2) and NO production were measured. The results show that mice fed a diet containing with fish oil had significantly decreased immunoglobulin G (IgG) anti-single strand (ss) or double strand (ds) DNA antibody levels, lessened proteinuria and prolonged life span compared to mice fed diets containing other types of dietary fat. TNF-alpha and PGE2 levels in mice fed a diet containing fish oil were significantly lower compared to the other dietary groups. IL-6 and NO produced by peritoneal resident cells were significantly higher in mice fed a diet containing lard/soybean oil in comparison with mice of the other groups. Hepatic ex vivo PGE2 level was significantly lower in mice fed fish oil compared to mice of the other dietary groups. These data suggested that dietary fish oil might affect either autoantibody production or macrophage function, contributing to alleviation of the autoimmune process in autoimmune-prone NZB/W F1 mice.
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PMID:Late feeding of dietary fish oil alleviates disease severity and affects macrophage function in autoimmune NZB/W F1 mice. 1091 76

Tubulointerstitial injury caused by multiple insults, including significant proteinuria, results in interstitial inflammation. Evidence supports the hypothesis that interstitial inflammatory cells initially recruited in response to injury subsequently contribute to interstitial fibrosis. Experimental manipulations that decrease the number of interstitial macrophages (Mphis) preserve renal function. Mphis have the potential to secrete a large number of products, including some with fibrosis-promoting effects. Their most potent profibrotic effect may be the production of soluble fibrogenic factors, such as transforming growth factor-ss, endothelin-1, and tumor necrosis factor-alpha. These factors stimulate the synthesis of extracellular matrix proteins by neighboring myofibroblasts. Mphis may also release inhibitors of such matrix-degrading proteases as tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1. Protease inhibitors have a role in renal scarring by impairing the process of matrix remodeling and degradation, which normally functions in parallel with matrix synthesis. It is predicted that therapeutic interventions that dampen the interstitial inflammatory response will attenuate the renal fibrogenic response, preserving normal renal architecture and function.
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PMID:Role of cellular infiltrates in response to proteinuria. 1115 57

Mycophenolate mofetil (MMF) is a new immunosuppressive drug whose active metabolite, mycophenolic acid (MPA), blocks the action of inosine monophosphate dehydrogenase, resulting in the inhibition of the novo purine synthesis. Thus, MPA has an antiproliferative effect on T and B lymphocytes and also inhibits the glycosylation of cell surface adhesion proteins involved in cell-cell contact and in the recruitment of circulating leukocytes to sites of tissue damage and inflammation. In this study, the effect of MMF in the mercury model of nephritis was examined. Repeated exposure to HgCl(2) induces an autoreactive Th2 cell subset-inducing polyclonal B cell activation in the Brown Norway (BN) rat. This leads to the development of an autoimmune syndrome characterized by synthesis of autoantibodies (mainly anti-glomerular basement membrane [GBM] Abs) with glomerular linear deposits of IgG, proteinuria, and tubulointerstitial nephritis. Results show that MMF has a preventive effect on mercury-induced disease as it blocks anti-GBM Ab synthesis, thus avoiding glomerular IgG deposits and proteinuria and the development of interstitial nephritis. However, the therapeutic effect of MMF seems to be restricted to its antiinflammatory properties blocking the extravasation of circulating leukocytes to renal interstitium by interfering with the very late activation antigen 4/vascular cell adhesion molecule-1 (VCAM-1) cell adhesion pathway. Also, MMF administration to mercury-injected rats reduces the secretion of the proinflammatory cytokine tumor necrosis factor-alpha. These findings confirm that MMF has a strong effect on the primary immune response in this model. Nevertheless, when the disease is in progress, MMF acts exclusively on the inflammatory response. MMF could be useful in the treatment of diseases associated with renal inflammation.
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PMID:Effects of mycophenolate mofetil in mercury-induced autoimmune nephritis. 1191 53

We investigated lymphocyte subpopulations and the production of cytokines by T helper cell subtype 1 (Th1), Th2, and monocytes/macrophages (tumor necrosis factor-alpha [TNF-alpha]) in peripheral-blood mononuclear cells of 18 children with steroid-sensitive (SS) nephrotic syndrome (NS) and 10 children with steroid-resistant (SR) NS. Mean age was 10.9 +/- 5.7 years, with a mean follow-up before the study of 6 +/- 5 years. To evaluate the possible relationship between cytokine levels and response to treatment, patients with SS and SR NS were assessed during relapse/marked proteinuria (group A), total/partial remission (group B), and off treatment (group C). In children with SS and SR NS, we found no significant difference in CD3 counts compared with controls. The proportion of CD4 cells decreased significantly in relapse and off therapy compared with controls in children with SS NS, whereas in those with SR NS, there was a concomitant reduction in all groups. B-Lymphocyte counts were significantly increased in either group versus controls. In SR NS, CD8 and natural killer cell levels increased during relapse versus controls. The CD4+/CD8+ ratio was reduced to the same degree in those with SS and SR NS. In patients with SR NS, we observed increased levels of soluble interleukin-2 (IL-2) receptor (sIL-2R) from corresponding control values (P < 0.01). A significant increase in TNF-alpha levels was found in patients with SS and SR NS versus controls. High levels of IL-2, sIL-2R, and interferon-gamma during relapse in patients with SS NS give further evidence for a Th1 pattern that might be involved in the pathogenesis of NS, and monitoring the Th1/Th2 balance would be useful in evaluating the response to therapy.
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PMID:T-lymphocyte populations and cytokines in childhood nephrotic syndrome. 1232 30

Risk factors for progression of kidney disease include hypertension, proteinuria, male sex, obesity, diabetes mellitus, hyperlipidemia, smoking, high-protein diets, phosphate retention, and metabolic acidosis. Angiotensin II production upregulates the expression of transforming growth factor-beta1, tumor necrosis factor-alpha, nuclear factor-kappaB, and several adhesion molecules and chemoattractants. In addition to angiotensin, other vasoactive compounds, such as thromboxane A(2), endothelin, and prostaglandins, are upregulated. Treatment with one of several growth factors may ameliorate the progression of kidney disease: insulin-like growth factor-1, hepatocyte growth factor, and bone morphogenetic protein-7.
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PMID:Progression of chronic renal disease. 1261 42

Proteinuria is an independent risk factor for progression of renal diseases. Glia maturation factor-beta (GMF-beta), a 17-kDa brain-specific protein originally purified as a neurotrophic factor from brain, was induced in renal proximal tubular (PT) cells by proteinuria. To examine the role of GMF-beta in PT cells, we constructed PT cell lines continuously expressing GMF-beta. The PT cells overexpressing GMF-beta acquired susceptibility to cell death upon stimulation with tumor necrosis factor-alpha and angiotensin II, both of which are reported to cause oxidative stress. GMF-beta overexpression also promoted oxidative insults by H2O2, leading to the reorganization of F-actin as well as apoptosis in non-brain cells (not only PT cells, but also NIH 3T3 cells). The measurement of intracellular reactive oxygen species in the GMF-beta-overexpressing cells showed a sustained increase in H2O2 in response to tumor necrosis factor-alpha, angiotensin II, and H2O2 stimuli. The sustained increase in H2O2 was caused by an increase in the activity of the H2O2-producing enzyme copper/zinc-superoxide dismutase, a decrease in the activities of the H2O2-reducing enzymes catalase and glutathione peroxidase, and a depletion of the content of the cellular glutathione peroxidase substrate GSH. The p38 pathway was significantly involved in the sustained oxidative stress to the cells. Taken together, the alteration of the antioxidant enzyme activities, in particular the peroxide-scavenging deficit, underlies the susceptibility to cell death in GMF-beta-overexpressing cells. In conclusion, we suggest that the proteinuria induction of GMF-beta in renal PT cells may play a critical role in the progression of renal diseases by enhancing oxidative injuries.
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PMID:Induction of glia maturation factor-beta in proximal tubular cells leads to vulnerability to oxidative injury through the p38 pathway and changes in antioxidant enzyme activities. 1279 1

Adenosine protects against cellular damage and dysfunction under several adverse conditions, including inflammation. We examined the effects of KF24345, a novel adenosine uptake inhibitor, on inflammatory diseases to investigate whether the adenosine uptake inhibition is useful for the treatment of inflammation. KF24345 inhibited adenosine uptake into washed erythrocytes (in vitro) and sampled blood cells from mice after its oral administration (in vivo). KF24345 significantly suppressed lipopolysaccharide-induced tumor necrosis factor-alpha production and leukopenia in mice, and the effects of KF24345 were abolished by the treatment with a non-selective or an A(2A)-selective adenosine receptor antagonist. In the experimental glomerulonephritis induced in mice by anti-glomerular basement membrane antiserum, KF24345 significantly inhibited proteinuria and glomerular damage without exhibiting the side effects observed following the treatment with prednisolone and cyclophosphamide. In addition, KF24345 ameliorated the severity of experimental acute pancreatitis induced by cerulein or choline-deficient and ethionine-supplemented diet in mice, and it decreased mortality accompanying severe acute pancreatitis. The anti-pancreatitis effects of KF24345 were abolished by the treatment with a non-selective or an A(2A)-selective adenosine receptor antagonist. These results suggest that KF24345 and adenosine uptake inhibitors can be a new therapeutic approach for various inflammatory diseases, including glomerulonephritis and acute pancreatitis.
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PMID:[Pharmacological study on the effects of the adenosine uptake inhibitor KF24345 on inflammatory diseases]. 1289 Aug 98

The pathogenetic mechanisms of IgA nephropathy are diverse and are not yet clearly elucidated. We believe pro-inflammatory cytokines, Th1/Th2, and chemokines would be involved in the pathogenetic pathways and would affect the functional and histological consequences of IgA nephropathy. By using semiquantitative reverse transcriptase-polymerase chain reactions (RT-PCR), we measured the level of intrarenal gene expression of various cytokines and chemokines in 61 renal core biopsy specimens confirmed as IgA nephropathy. And, by using immunohistochemistry (IHC), the degree of expression and the location of various cytokines and chemokines in renal tissues in 29 of the above patients were attempted to be determined. In RT-PCR, the gamma-interferon (IFN-gamma)/interleukin-10 (IL-10) ratio was higher in patients with renal dysfunction than in those with normal renal function. The levels of pro-inflammatory cytokine gene transcripts (tumor necrosis factor-alpha (TNF-alpha), IL-1beta) were high in patients with significant proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN-gamma/IL-10 gene transcripts was high. The level of IL-10 gene transcript was related to the severity of tubular atrophy and interstitial fibrosis. The extent of intrarenal arteriolar lesions correlated with the expression of the IL-8 gene transcript. The degree of IgA deposition in glomeruli was related to the expression of IL-15 and IL-6. In IHC, TNF-alpha, IFN-gamma and IL-2 were immunostained dominantly in the mesangial region, but not in the tubulointerstitial region. In contrast, positive reactions for IL-10 were observed primarily in tubules. Significant reactions for IL-8 were noted in the periarteriolar and arteriolar areas. The results of RT-PCR and IHC showed positive relationships, but these were not statistically significant. This study suggests that pro-inflammatory, Th1/Th2 cytokines and chemokines are involved in the specific processes of inflammation and immunological injury in IgA nephropathy.
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PMID:Clinicopathological correlation of intrarenal cytokines and chemokines in IgA nephropathy. 1501 46

Anti-inflammatory properties of pentoxifylline (PTX) have recently been described. Spontaneously hypertensive stroke-prone rats (SHRSP) constitute an animal model that develops an inflammatory condition that precedes the appearance of brain abnormalities. The aim of the present investigation was to assess: 1) the efficacy of PTX treatment in protecting the neural system in SHRSP, and 2) how its anti-inflammatory properties might be involved in this effect. Male SHRSP fed with a permissive diet received no drug or PTX (100 or 200 mg/kg/day). Brain abnormalities detected by magnetic resonance imaging developed spontaneously in control rats after 42 +/- 3 days, whereas in rats treated with 100 mg/kg/day PTX, abnormalities developed in only 80% of the animals and only after 70 to 80 days. Treatment with a higher dose of PTX (200 mg/kg/day) completely protected the brain from abnormal development. The drug treatment prevented the accumulation of macrophages or CD4+ positive cells, the activation of glia in brain tissues, and the appearance of inflammatory proteins and thiobarbituric acid-reactive substances in body fluids. PTX treatment did induce a greater increase of serum tumor necrosis factor-alpha (TNF-alpha), but not of interleukin (IL)-1beta and IL-6 induced by in vivo administration of lipopolysaccharide (LPS), which suggests a protective role for TNF-alpha. PTX also exerted protective effects when it was administered after the first occurrence of proteinuria (>40 mg/day). These data indicate that PTX treatment dose-dependently prevents the occurrence of spontaneous brain damage by reducing inflammatory events. We also hypothesize that the increase of TNF-alpha by PTX treatment represents a protective mechanism in SHRSP.
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PMID:Pentoxifylline prevents spontaneous brain ischemia in stroke-prone rats. 1520 42

Epidemiological studies have shown strong associations between silica exposure and several autoimmune diseases, including scleroderma and systemic lupus erythematosus. We previously reported that the New Zealand mixed (NZM) mouse develops silicosis and exacerbated autoimmunity following crystalline silica exposure, including increased levels of autoantibodies, proteinuria, circulating immune complexes, pulmonary fibrosis, and glomerulonephritis. In this study, the NZM mouse was used to examine changes in immune activation following silica exposure by measuring levels of immunoglobulin, cytokines and lymphocyte populations. Levels of immunoglobulin (Ig) G1 were significantly decreased from 1124 +/- 244 microg/ml in saline exposed mice to 614 +/- 204 microg/ml in silica-exposed mice, suggesting a decrease in the Th2 response. The levels of tumor necrosis factor (TNF)-alpha were significantly increased (1.5-fold) in the bronchoalveolar lavage fluid of the silica-exposed mice as compared to the saline-exposed mice. The number of B1a B cells were significantly increased sixfold within the superficial cervical lymph nodes of silica-exposed mice as compared with saline-exposed mice. Following silica exposure, CD4+ T cells significantly increased threefold within the superficial cervical lymph nodes. During this increase in the number of CD4+ T cells, the number of CD4+CD25+ regulatory T cells was not significantly changed, altering the ratio of regulatory T cells to T helper cells from 1:5 to 1:8 following silica exposure. Therefore, the silica-induced alterations in immunoglobulin levels, increased TNF-alpha, increased B1a B cells and CD4+ T cells, with decreased regulatory T cells, may provide an environment that allows for increased autoreactivity. These studies begin to provide possible mechanisms for environmentally induced autoimmune diseases that have been reported in many epidemiological studies.
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PMID:Immunoglobulin and lymphocyte responses following silica exposure in New Zealand mixed mice. 1520 74


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