Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mesangial cell proliferation constitutes a frequent finding in a number of glomerular diseases that progress to glomerular sclerosis. The factors responsible for mesangial cell growth regulation in vivo are ill defined. However, cell culture data indicate that an array of mediators may have mitogenic or antimitogenic effects on these cells. This brief review discusses the relevance of selected factors such as platelet-derived growth factor (PDGF) in this context. In vitro data indicate that PDGF is one of the most potent mesangial cell mitogens, that it may have autoregulatory properties, and that it may represent the final common pathway for a number of other mitogenic peptides. In contrast to PDGF, the relevance of inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF) or interleukin-6 (IL-6) for mesangial cell proliferation is less evident, with growth-inhibitory to weakly growth-promoting effects on mesangial cells. Transforming growth factor beta (TGF beta) appears to be unique in that it has a concentration-dependent mitogenic or antimitogenic effect on mesangial cells. Prostaglandins may also have variable effects, ranging from mitogenic (PGE2 alpha) to growth inhibitory (PGI2, PGF2, TxA2). These data support the notion that mesangial cell growth in vivo is regulated by a complex network of synergistic or antagonistic growth factors. The relative importance of each of these growth factors in the in vivo situation will have to be elucidated by future studies using specific receptor antagonists or neutralizing antibodies.
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PMID:Regulation of mesangial cell proliferation. 204 47

Interleukin-6 (IL-6) is a pleiotropic cytokine that has been postulated as playing a role in the pathogenesis of multiple myeloma, chronic autoimmune diseases, and alcoholic liver cirrhosis. We generated transgenic mice carrying a fusion between the mouse metallothionein-I (MT-I) gene promoter and the human IL-6 cDNA. MT-I/IL-6 transgenics express IL-6 constitutively in the liver and secrete the cytokine in the blood. They show initially activation of acute-phase response genes and accumulation of alpha 2- and beta-globulins in the plasma, which is followed by polyclonal hypergammaglobulinemia. MT-I/IL-6 transgenics die between 12 to 20 weeks of age. Histologic examination of transgenic animals at different ages and after necropsy showed, as expected from previous studies of IL-6 disregulation in vivo, an increase in the number of megakaryocytes in the spleen and bone marrow and, at later stages, IgG plasmacytosis in the spleen, lymph nodes, and thymus. However, no plasma cell infiltration was detected in other organs. The distinguishing feature of MT-I/IL-6 transgenics is the development of a progressive kidney pathology, in which the initial membranous glomerulonephritis is followed by focal glomerulosclerosis and finally by extensive tubular damage that reproduces the damage observed in patients at terminal stages of multiple myeloma (myeloma kidney). The pathogenetic role of IL-6 overproduction and of the resulting serum protein overload in the kidney damage is discussed.
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PMID:Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice. 751 4

Human immunodeficiency virus infection is associated with the development of focal segmental glomerulosclerosis (FSGS). The majority of these patients with renal disease, however, are also cocaine abusers, but it is unknown what role cocaine may play in the development of focal segmental glomerulosclerosis. We undertook the present study to determine in vitro whether cocaine can modulate mesangial cell (MC) proliferation, a process believed to be a precursor to the development of glomerulosclerosis, either directly or indirectly via interaction with macrophages (M phi). Cocaine alone was not found to alter significantly either MC number or MC [3H]thymidine incorporation. However, when MC were incubated with secretory products collected from M phi preincubated with standard medium or medium containing cocaine, MC proliferation was found to be significantly enhanced with secretory products from M phi preincubated with cocaine in both serum-free (P < .001) and serum-stimulated conditions (P < .001). The effect of cocaine was found to be concentration-related. Pretreatment of macrophage secretory products from cocaine-treated M phi with neutralizing antibodies to transforming growth factor-beta significantly augmented the mitogenic effect of cocaine macrophage secretory products, and neutralizing antibodies to interleukin-6 significantly attenuated this effect. Direct incubation of MC with transforming growth factor-beta and interleukin-6 caused significant suppression and augmentation of MC proliferation, respectively. These data suggest that cocaine can modulate MC proliferation via interaction with M phi and that interleukin-6 and transforming growth factor-beta participate in this modulating effect. These results support a potential role for cocaine in the development of focal segmental glomerulosclerosis in patients with human immunodeficiency virus infection.
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PMID:Cocaine interacts with macrophages to modulate mesangial cell proliferation. 796 30

Serum and urinary tumor necrosis factor-alpha (SeTNF and UTNF) and interleukin-6 (SeIL-6 and UIL-6) by ELISA method were determined in 99 patients with glomerulonephritis (GN): 13 with extracapillaris GN (ExGN), 38 with membranoproliferative GN (MPGN), 33 mesangial proliferative GN (MesPGN), 5 with focal segmental glomerulosclerosis (FSGS), 5 with membranous nephropathy (MN), 3 with minimal change nephropathy (MC) and in 32 healthy adults. The higher levels of Se TNF than those in the healthy were in 25 patients: in nearly all with ExGN, in 8 with MPGN and in single patients with other GN. In all patients with high SeTNF were many extra renal organs involvement. Measurable levels of UTNF were in 30 patients (30%) (in 12 with ExGN, 9 with MPGN, 7 with MesPGN, 1 with MN, and 1 with FSGS). Most patients with high SeTNF belonged to group I. The higher levels of SeIL-6 than those in healthy were in 17 patients belonging to group I, in which high SeIL-6 were in 3 patients with ExGN, 6 with MPGN, 3 with MesPGN, 2 with MN, and 3 with FSGS. Measurable urinary IL-6 levels were in 27 (27%) patients, mainly in group I, and in single patients in other groups. The majority of patients with ExGN and MPGN from group I and UIL-6 positive suffered from renal insufficiency and histologically had proliferative GN. We conclude that the elevation of TNF alpha and/or IL-6 in plasma may reflect a secondary consequence of immune cells activation while urinary TNF alpha and/or IL-6 may be secreted by activated glomerular cells. Thus, high levels of TNF alpha and/or IL-6 in serum of patients with GN and extra renal organs involvement, peculiary with infections, suggested antibiotics therapy, because infection may stimulated cytokines production and they are important in pathogenesis and progress of GN. High urinary levels of IL-6 and (or) TNF alpha in patients with proliferative GN suggest great disease activity and is useful in the evaluating of IS treatment.
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PMID:[Tumor necrosis factor (TNF) and interleukin-6 (IL-6) in patients with glomerulonephritis]. 912 13

Low-density lipoprotein (LDL) may contribute to the pathogenesis of glomerulosclerosis by stimulating a mesangial cell inflammatory response. Interleukin-6 (IL-6) is a marker of active inflammation and ongoing glomerular injury. Therefore, we investigated the effects of native and oxidized LDL on human mesangial cell production of IL-6 and a possible modulation of this inflammatory response by lovastatin, which has been shown to ameliorate experimental glomerulosclerosis. Human mesangial cells were exposed for 6 or 24 h to culture medium containing either native LDL alone or a LDL mixture containing 5 or 20% oxidized LDL. We found that native LDL stimulated 6 h mRNA expression and secretion of IL-6. This effect was further enhanced, in a dose-related manner, when mesangial cells were exposed to increasing concentrations of oxidized LDL. Lovastatin markedly inhibited mesangial cell expression of IL-6 mRNA and reduced IL-6 secretion. The inhibitory effects of lovastatin were overridden at least partially by exogenous mevalonate. We conclude that LDL, and particularly oxidized LDL, might contribute to the pathogenesis of glomerular disease by modulating the inflammatory response of human mesangial cells, as assessed by the stimulation of IL-6 expression. Moreover, this inflammatory response can be prevented by lovastatin, providing a potential direct anti-inflammatory mechanism by which HMG-CoA reductase inhibitors may attenuate lipid-induced glomerular injury.
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PMID:Low-density lipoprotein-induced expression of interleukin-6, a marker of human mesangial cell inflammation: effects of oxidation and modulation by lovastatin. 1063 Oct 97

Few studies have examined the role of the microvasculature in progressive renal disease. It was hypothesized that impaired angiogenesis might occur in the diseased kidney and could contribute to renal scarring. Progressive renal disease was induced in rats by 5/6 renal ablation and those rats were compared with sham-operated control animals at multiple time points, for examination of changes in the microvasculature and the expression of angiogenic factors. An early angiogenic response was documented in remnant kidneys, with increases in the proliferation of peritubular (1 wk) and glomerular (2 wk) endothelial cells. Subsequently, however, there was a decrease in endothelial cell proliferation, which was reduced to levels below those of sham-treated animals, in conjunction with interstitial expression of the antiangiogenic factor thrombospondin-1 (TSP-1) and decreased tubular expression of the proangiogenic factor vascular endothelial growth factor (VEGF). Both the increase in TSP-1 expression and the loss of VEGF expression were correlated with capillary loss and the development of glomerulosclerosis and interstitial fibrosis. Progressive macrophage infiltration was correlated both spatially and quantitatively with the sites of absent or diminished VEGF expression. In addition, macrophage-associated cytokines (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha) inhibited VEGF mRNA expression and protein secretion by cultured tubular epithelial cells of the medullary thick ascending limb, under both normoxic and hypoxic conditions. Impaired angiogenesis characterizes the remnant kidney model and is correlated with progression. The impaired angiogenesis may be mediated by alterations in the renal expression of TSP-1 and VEGF, with the latter being regulated by macrophage-associated cytokines.
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PMID:Impaired angiogenesis in the remnant kidney model: I. Potential role of vascular endothelial growth factor and thrombospondin-1. 1142 72

When a 63-year-old man was hospitalized with nephrotic syndrome due to focal segmental glomerulosclerosis, a mediastinal mass was discovered. A biopsy specimen obtained by mediastinoscopy showed findings compatible with the plasma cell type of Castleman's disease. Fever, anemia, and anti-nuclear antibody were present. Serum concentrations of gamma globulin, acute phase proteins, and, most strikingly, interleukin-6 (IL-6) were elevated. Methylprednisolone pulse therapy resulted in no clinical improvement. Pathologic examination of the resected thymic tumor showed a squamous cell carcinoma immunoreactive for IL-6. To our knowledge, this case represents the first reported IL-6-producing thymic squamous cell carcinoma associated with Castleman's disease and nephrotic syndrome.
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PMID:Interleukin-6-producing thymic squamous cell carcinoma associated with Castleman's disease and nephrotic syndrome. 1241 13

The advanced glycation end products (AGEs) are a heterogeneous class of molecules, including the following main subgroups: bis(lysyl)imidazolium cross-links, hydroimidazolones, 3-deoxyglucosone derivatives, and monolysyl adducts. AGEs are increased in diabetes, renal failure, and aging. Microvascular lesions correlate with the accumulation of AGEs, as demonstrated in diabetic retinopathy or renal glomerulosclerosis. On endothelial cells, ligation of receptor for AGE (RAGE) by AGEs induces the expression of cell adhesion molecules, tissue factor, cytokines such as interleukin-6, and monocyte chemoattractant protein-1. A chief means by which AGEs via RAGE exert their effects is by generation of reactive oxygen species, at least in part via stimulation of NADPH oxidase. Diabetes-associated vascular dysfunction in vivo can be prevented by blockade of RAGE. Thus, agents that limit AGE formation, increase the catabolism of these species, or antagonize their binding to RAGE may provide new targets for vascular protection in diabetes.
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PMID:Protein glycation: a firm link to endothelial cell dysfunction. 1529 85

Intrauterine growth retardation (IUGR) aggravates the course of acute mesangioproliferative glomerulonephritis (GN) in the rat. Observational studies in children suggest that IUGR may be associated with a severe course of kidney diseases such as IgA nephropathy. We tested the hypothesis that IUGR leads to aggravation of acute mesangioproliferative GN in former IUGR rats. IUGR was induced in Wistar rats by isocaloric protein restriction in pregnant dams. Litter size was reduced to six male neonates in low protein animals (LP) and normal protein animals (NP). At 8 weeks GN was induced by injection of an anti-Thy-1.1 antibody. Rats were killed on days 4 and 14 after induction of GN and kidneys were investigated for inflammation and sclerosis using real-time polymerase chain reaction and histological methods. On day 4 after induction of GN, LP animals showed more glomerulosclerosis and tubulointerstitial lesions. On day 14, inflammatory markers (expression of monocyte chemoattractant protein 1, osteopontin, tumor necrosis factor and interleukin-6), extracellular matrix accumulation and markers of sclerosis (plasminogen activator inhibitor-1 expression, transforming growth factor-beta1 expression, score for glomerulosclerosis, glomerular deposition of collagen I and collagen IV) were more severe in LP animals. Some degree of induction of inflammatory and profibrotic markers was also present in non-nephritic LP animals. However, these rats did not display marked glomerulosclerosis or interstitial fibrosis. We conclude that after IUGR inflammatory damage is aggravated and the reparation of the kidney is impaired during the course of acute mesangioproliferative GN, leading to more sclerotic lesions.
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PMID:Intrauterine growth retardation aggravates the course of acute mesangioproliferative glomerulonephritis in the rat. 1705 Nov 40

The effect of interleukin-6 (IL-6) on gene expression of extracellular matrix components in bovine mesangial cells in culture has been investigated. IL-6 (100 U/ml) time dependently increased the steady state expression of mRNAs coding for alpha1 collagen III and fibronectin, both transcripts being 1.5- and 2.5-fold higher than basal level at 24 and 48 h, respectively. In contrast, IL-6 stimulated laminin mRNA expression only after 48 h incubation (2.5-fold upon basal level). These results suggest that IL-6 could favour glomerular matrix accumulation thus contributing to the development of glomerulosclerosis.
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PMID:Interleukin-6 stimulates gene expression of extracellular matrix components in bovine mesangial cells in culture. 1847 59


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