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)

Chemokines are low molecular weight inflammatory cytokines with chemoattractant properties as their major biologic effect. They are classified into at least two families. C-X-C chemokines (alpha subfamily) act primarily on neutrophils, while C-C chemokines act preferentially on monocytes. Chemokine receptors are G protein-coupled receptors that form a family of structurally and functionally related proteins. Chemokines are induced in cells and tissue in response to proinflammatory cytokines. They are produced by glomerular, tubular interstitial, and blood vessel cells. There is good evidence that chemokines contribute to neutrophil and mononuclear cell infiltration in glomeruli and interstitium. Their expression is increased in renal disease, and neutralization studies using antibodies in vivo demonstrated a role for certain chemokines in mediating renal pathology and proteinuria. Interleukin-8, RANTES, and monocyte chemotactic peptide are the best-studied chemokines in the kidney. Development of specific antibodies and receptor antagonists should help establish the precise role of these mediators in renal disease. Important therapeutic implications may result from this work.
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PMID:Chemokines and renal disease. 750 75

Chemokines are a family of cytokines whose participation in inflammation in vivo remains to be established. Using the rat model of anti-glomerular basement membrane (GBM) nephritis, we found that mRNA for the chemokine CINC (cytokine-induced neutrophil chemoattractant) was induced in the kidney, and the corresponding protein was elaborated by isolated inflamed glomeruli. Production of CINC by glomeruli was unaffected by complement- or leukocyte-depletion prior to disease induction. Cytokines which induce CINC expression in renal cells (TNF-alpha and IL-1 beta) were also expressed in the kidney during glomerular inflammation. TNF-alpha production, unlike CINC, was complement and leukocyte dependent. In vivo administration of anti-CINC, but not anti-human IL-8, IgG selectively attenuated the influx of PMNs into the glomerulus and commensurately diminished proteinuria. The participation of CINC was not tissue-specific: anti-CINC IgG also diminished the influx of PMNs in dermal immune complex inflammation. In sum, we propose that glomerular immune complex deposition/complement activation leads to cytokine production which results in CINC expression by endogenous glomerular cells. The CINC produced plays a contributory role in the influx of PMNs into the glomerulus in the context of the activation of other inflammatory mediators. These results suggest a potential role for CINC homologues, IL-8 and the GRO family of chemokines, in human immune complex-mediated disease.
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PMID:Cytokine-induced neutrophil chemoattractant mediates neutrophil influx in immune complex glomerulonephritis in rat. 804 Feb 75

We studied mRNA and protein expression of interleukins (IL) and tumor necrosis factor (TNF) in renal tissues biopsied from 40 patients with IgA nephritis. Immunofluorescent staining with antibodies to IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta was intense in the cytoplasm of cells in glomeruli, which were dual-stained with an anti-monocyte-macrophage antibody. In addition, moderate immunofluorescence for TNF-alpha, and weak staining for IL-1 alpha and IL-6 were occasionally found in resident glomerular cells. Immunoperoxidase-in situ hybridization dual-labeling revealed that IL-1 alpha, IL-6, and TNF-alpha mRNA signals were present in intraglomerular cells reactive with anti-monocyte-macrophage antibody, which further supported the immunofluorescent findings. Cells expressing IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta were also observed in the interstitium. Most of these cells were also labeled with the anti-monocyte-macrophage antibody. The number of IL-1 alpha, IL-6, and TNF-alpha-positive cells infiltrating the glomerulus significantly correlated with mesangial hypercellularity. IL-8 and TNF-alpha-positive intraglomerular cells were correlated with the magnitude of proteinuria. The population of interstitial cells positive for IL-1 alpha, IL-6, IL-8, and TNF-alpha was associated with the grade of tubulointerstitial changes and proteinuria. There was no correlation between local IL-1 alpha, IL-6, and TNF-alpha expression in glomeruli or interstitium and serum or urinary levels of the respective cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In situ expression of cytokines in IgA nephritis. 825 57

A case in which the enterotoxins of Staphylococcus aureus may have served as bacterial superantigens is presented. This 71-year-old man developed proteinuria and renal dysfunction after contacting pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), coagulase type II. The infection occurred after surgery for recurrent lung cancer. Staphylococcus enterotoxins B, C, and TSST-1 were detected from the bacillus. Ten days after the onset of pneumonia, proteinuria was noted; urinary protein was as high as 1.8 g/day. The serum creatinine was elevated from 1.0 mg/dl to 3.7 mg/dl. Several immunological reactions were detected; the serum levels of IgG and IgA were increased, and the selective usage of T-cell receptor V beta (TCRV beta) was observed. Serum levels of IL-1 beta, IL-2, IL-6, IL-8, IL-12, and tumor necrosis factor alpha (TNF alpha) were also elevated. Examination of the renal biopsy specimen by light microscopy showed minor to mild mesangial proliferative glomerulonephritis. Immunofluorescence microscopy demonstrated the deposition of IgG, IgA, and C3, mainly along the capillary walls. Electron microscopy revealed electron dense deposits, mainly in the subepithelial areas, and injury to the glomerular basement membrane. When the pneumonia improved following antibiotic therapy, the renal function also improved, and proteinuria decreased. The levels of immunoglobulins and the usage of TCRV beta also decreased. Because staphylococcus enterotoxins act as superantigens, we believe this to be a typical case of superantigen-related glomerulonephritis.
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PMID:A case of superantigen-related glomerulonephritis after methicillin-resistant Staphylococcus aureus (MRSA) infection. 940 16

A 20-year-old woman with arthralgia, serositis, thrombocytopenia, proteinuria, muscle weakness, elevated creatinine kinase, and positive anti-Sm antibody was diagnosed as having polymyositis and systemic lupus erythematosus (SLE). She had persistent high temperature, sinus tachycardia, hyperhidrosis, mydriasis, visual disturbance, hallucination, and loss of consciousness. Levels of plasma adrenaline, noradrenaline, and dopamine and cerebrospinal fluid interleukin (IL)-6 and IL-8 were all high. A diagnosis of sympathetic hyperfunction accompanied by central nervous system (CNS) involvement in SLE was made parenteral. Pulse administration of high dose corticosteroid therapy was effective. This is the first reported case of a connective tissue disease with CNS involvement manifesting as sympathetic hyperfunction with high plasma catecholamine levels.
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PMID:Acute sympathetic hyperfunction in overlapping syndromes of systemic lupus erythematosus and polymyositis. 971 13

In many diseases and acute inflammatory disorders, important components of pathological processes are linked to the neutrophils' ability to release a complex assortment of agents that can destroy normal cells and dissolve connective tissue. This review summarizes the mechanisms of tissue destruction by neutrophils and the role of kidney-specific factors that promote this effect. Nicotinamide adenine dinucleotide phosphate H (NADPH) oxidase is a membrane-associated enzyme that generates a family of reactive oxygen intermediates (ROI). There is increasing evidence that ROIs are implicated in glomerular pathophysiology: ROIs contribute to the development of proteinuria, alter glomerular filtration rate, and induce morphological changes in glomerular cells. Specific neutrophil granules contain microbicidal peptides, proteins, and proteolytic enzymes, which mediate the dissolution of extracellular matrix, harm cell structures or cell function, and induce acute and potentially irreparable damage. Although both ROI and neutrophil-derived proteases alone have the potential for tissue destruction, it is their synergism that circumvents the intrinsic barriers designed to protect the host. Even small amounts of ROI can generate hypochlorus acid (HOCl) in the presence of neutrophil-derived myeloperoxidase (MPO) and initiate the deactivation of antiproteases and activation of latent proteases, which lead to tissue damage if not properly controlled. In addition, neutrophil-derived phospholipase products such as leukotrienes and platelet-activating factor contribute to vascular changes in acute inflammation and amplify tissue damage. Increasing evidence suggests that mesangial cells and neutrophils release chemotactic substances (eg, interleukin 8), which further promote neutrophil migration to the kidney, activate neutrophils, and increase glomerular injury. Also, the expression of adhesion molecules (eg, intercellular adhesion molecule 1 on kidney-specific cells and beta-2-integrins on leukocytes) has been correlated with the degree of injury in various forms of glomerulonephritis or after ischemia and reperfusion. Together, these results suggest that neutrophils and adhesion molecules play an important role in mediating tissue injury with subsequent renal failure. Conversely, chronic renal failure reduces neutrophil function and thereby can increase susceptibility to infection and sepsis.
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PMID:Neutrophils and renal failure. 1043 Sep 93

Blocking chemokine production or action is a major target for pharmacological intervention in different human diseases. Bindarit (2-methyl-2-[[1-(phenylmethyl)-1H-indazol-3yl]methoxy]propan oic acid) dose-dependently inhibited MCP-1 and TNF-alpha production induced in vitro in monocytes by LPS and Candida albicans. It did not affect the production of the cytokines IL-1, IL-6, or the chemokines IL-8, MIP-1alpha and RANTES. In the air pouch model in mice, oral treatment reduced monocyte recruitment and local MCP-1 production, induced by carrageenan or IL-1 injection. In NZB/W mice, a model of lupus nephritis, oral treatment prolonged survival and delayed the onset of proteinuria. The results presented here show that bindarit is a preferential inhibitor of the production of MCP-1 in vitro and in vivo and suggest that its beneficial effects in models of joint and kidney inflammation are related to its anti-MCP-1 action. It is therefore possible to selectively and differentially regulate chemokines by targeting their production with small synthetic molecules.
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PMID:A small synthetic molecule capable of preferentially inhibiting the production of the CC chemokine monocyte chemotactic protein-1. 1047 1

An 18-year-old woman developed subacute transverse myelopathy with renovascular hypertension, hyperlipidemia, and proteinuria. Spinal magnetic resonance imaging(MRI) showed an intra-spinal cord lesion with severe spinal cord swelling at the C 2-Th 2 level. Increased plasma and cerebrospinal fluid interleukin-8(IL-8) levels and the presence of serum antineutrophil cytoplasmic antibody(ANCA) suggested the existence of an ischemic lesion due to vasculitis. Administration of corticosteroids ameliorated the clinical symptoms and MRI findings. Renovascular angiogram revealed the presence of fibromuscular dysplasia(FMD) at the left renal artery but no malformation was found at the cervical arteries. We discussed the possibility of relationships between myelopathy, FMD, IL-8, and ANCA.
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PMID:[Transverse myelopathy with renovascular hypertension caused by fibromuscular dysplasia]. 1159 81

Chemokines and their receptors play an important role in the pathogenesis of acute and chronic glomerular inflammation. However, their expression pattern and function in glomerular podocytes, the primary target cells in a variety of glomerulopathies, have not been investigated as of yet. Using RT-PCR, we now demonstrate the expression of CCR4, CCR8, CCR9, CCR10, CXCR1, CXCR3, CXCR4, and CXCR5 in cultured human podocytes. Stimulation of these receptors induced a concentration-dependent biphasic increase of the free cytosolic calcium concentration in podocytes in culture. In addition, we demonstrate that podocytes release IL-8 in the presence of FCS and that IL-8 down-regulates cell surface CXCR1. Chemokine stimulation of the detected CCRs and CXCRs increased activity of NADPH-oxidase, the primary source of superoxide anions in podocytes. Immunohistochemistry studies revealed only diffuse and weak CXCR expression in healthy human glomerula. In contrast, in membranous nephropathy, a characteristic podocyte disorder, the expression of CXCR1, CXCR3, and CXCR5 is up-regulated in podocytes. In conclusion, podocytes in culture and podocytes in human kidney sections express a set of chemokine receptors. The release of oxygen radicals that accompanies the activation of CCRs and CXCRs may contribute to podocyte injury and the development of proteinuria during membranous nephropathy.
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PMID:Expression of functional CCR and CXCR chemokine receptors in podocytes. 1205 38

Renal proximal tubular epithelial cells (PTEC) are target for LPS during sepsis and renal infections. In the present study, we evaluated whether stimulation of human PTEC by LPS is modulated through the soluble or the membrane form of the LPS receptor CD14. We found that PTEC lacked expression of the membrane form of CD14 and did not release soluble CD14 (sCD14). sCD14 was detected in the urine of normal subjects and it was increased in patients with renal sepsis or with proteinuria. In the presence of sCD14 and LPS binding protein (LBP), PTEC were 10 to 100-fold more sensitive to LPS activation, resulting in cytokine production (IL-6, IL-8 and TNF-alpha) and NO release. We found that sCD14 purified from urine was biologically active on PTEC. Moreover, the presence of sCD14 and LBP was required for cytotoxicity induced by low concentrations of LPS (1-10 ng/ml) in PTEC. Cell death showed the characteristics of both necrosis and apoptosis, as demonstrated by LDH release and by TUNEL and acridine orange staining and caspase-3 activation. Whereas the LPS alone was sufficient to induce necrosis, sCD14 and LBP were required for apoptosis. Our results suggest that sCD14 excreted in urine may participate with endotoxin in the activation and injury of renal proximal tubules. In particular, sCD14 may contribute to the tubulo-interstitial injury in clinical settings characterised by proteinuria and enhanced susceptibility to infections such as in diabetes.
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PMID:Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS. 1223 91


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