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)

A 51-year-old male who had been working as a building wrecker for 20 years, was admitted to our hospital in June 1999 for proteinuria and hematuria examination. He started this work in 1978. Twelve years later, severe coughing and bloody sputum began and he was diagnosed as having silicosis in 1995. Urinalysis on admission showed proteinuria(294 mg/day), microhematuria(20-30/hpf), RBC cast and granular cast. High serum IgA(770 mg/dl) and high serum interleukin-6(IL-6) (3,280 pg/dl) were found. A renal biopsy showed mild mesangial matrix expansion and mesangial cell proliferation with IgA deposition, which was diagnosed as IgA nephropathy. Chest X-rays showed multiple small nodular lesions on both lung fields indicating silicosis. In Nov. 1999, he resigned from his job as a building wrecker because of increasing coughing and bloody sputum associated with body weight loss. Within 3 months after stopping this work, coughing and bloody sputum disappeared and the abnormal urinalysis findings returned to normal. Serum IgA and serum IL-6 data improved to 462 mg/dl and 2.5 pg/dl, respectively. It is suggested that silicon exposure might be related to the pathogenesis of IgA nephropathy in this patient.
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PMID:[A case of IgA nephropathy associated with silicosis]. 1172 60

The therapeutic effect of M-2000 (C6H10O7) molecule was tested in Adriamycin-induced nephropathy. To induce experimental nephrosis, Adriamycin was given once by a single intravenous injection (7.5 mg/kg) through the tail vein. Six days after injection of Adriamycin, therapeutic protocol was developed by intraperitoneally (i.p) administration of 30 mg/kg M-2000 solution. Total of i.p. injections were 14, in which five injections were made every day and nine injections were carried out at regular 48-h intervals. Therapeutic protocol was terminated on day 28 and animals were killed on day 43. The treated patient rats showed a significant reduction in proteinuria, BUN, serum creatinine and serum cholesterol, as well as, administration of M-2000 could significantly diminish the serum level of interleukin-6 (IL-6) in treated animals compared to non-treated controls. Moreover, treatment with M-2000 significantly reduced number of glomerular leukocytes, Hypercellularity and hydropic change in capillary network within the renal cortex and decreased tubular casts. These data suggest that M-2000 therapy can ameliorate proteinuria, and suppress the progression of glomerular lesions in experimental model of nephrosis.
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PMID:M-2000, as a new anti-inflammatory molecule in treatment of experimental nephrosis. 1565 9

All-trans-retinoic acid (ATRA), a vitamin A derivative, was reported to suppress the interleukin-6 (IL-6) production and to downregulate the IL-6 receptor (IL-6R) and/or its signal transducer glycoprotein 130. We investigated the in vivo antinephritic effect of ATRA on IL-6 transgenic mice which had developed mesangial proliferative glomerulonephritis (PGN) as well as its in vitro inhibitory effect on the proliferation of rat mesangial cells. In vivo experiments on IL-6 transgenic mice showed that ATRA administration suppressed proteinuria and hematuria and reduced the IL-6 concentrations; furthermore, histological examination demonstrated that it improved PGN. In vitro experiments using rat mesangial cells demonstrated that ATRA inhibited cell growth in a dose-dependent manner within a range from 10(-4) to 10(-6) M. This inhibition by ATRA was partially counteracted by the addition of IL-6. RT-PCR assay results showed that ATRA also reduced IL-6R, but not the glycoprotein 130 expression in mesangial cells. These findings indicate that, by blocking of the IL-6 function, ATRA may be therapeutically effective in PGN.
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PMID:All-trans-retinoic acid inhibits the development of mesangial proliferative glomerulonephritis in interleukin-6 transgenic mice. 1579 17

Nuclear Factor-kappaB (NF-kappaB) has been suggested to play a role in the cellular and molecular mechanisms underlying glomerular injury. We investigated the potential role of NF-kappaB activation in the pathogenesis of glomerular injury in 31 patients with class III-V lupus nephritis (LN), 14 patients with non-proliferative proteinuric glomerulopathy and six normal controls. The expression of NF-kappaB subunits p65 and p50, and the NF-kappaB regulated proinflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) as well as CD68 and synaptopodin was examined by Southwestern histochemistry (SWH) or immunohistochemistry. In contrast to non-proliferative glomerulopathy and normal controls, NF-kappaB activation (both p65 and p50) was enhanced in glomerular endothelial, mesangial cells or infiltrating cells in class IV LN, along with upregulation of TNF-alpha, IL-1beta, IL-6 and ICAM-1 expression. Glomerular endothelial and mesangial activation of NF-kappaB and mesangial ICAM-1 expression correlated with disease activity and the level of glomerular macrophage infiltration. Podocyte NF-kappaB overactivation (predominantly p65) paralleled podocyte expression of TNF-alpha and IL-1beta in patients with LN and non-proliferative glomerulopathy. Podocyte staining scores of NF-kappaB and p65 were positively correlated with the severity of proteinuria in LN and non-proliferative glomerulopathy. These results suggest a pathogenic role for NF-kappaB in glomerular injury by multiple mechanisms.
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PMID:In situ glomerular expression of activated NF-kappaB in human lupus nephritis and other non-proliferative proteinuric glomerulopathy. 1620 45

Preeclampsia is a multisystem disorder manifest by hypertension after 20 weeks' gestation associated with end organ damage, usually proteinuria. The placenta is thought to be pivotal in the pathogenesis of the disease. Both the placenta and the maternal systemic response are characterised by heightened inflammation. Garlic has been shown to have anti-inflammatory and pro-apoptotic properties amongst others. It was hypothesised that treating placental explants with garlic may inhibit the production of inflammatory cytokines (interleukin-6 (IL-6) and tumour necrosis factor (TNFalpha)) and stimulate the production of anti-inflammatory cytokines (interleukin-10 (IL-10)) by the placental explants. Garlic, we hypothesised, would also stimulate apoptosis in the explants as measured by soluble TNF-related apoptosis-inducing ligand/Apo-2L (sTRAIL) production. Normal placental explants (n=5) and explants from women who had preeclampsia (n=4) were cultured in the presence of various garlic concentrations (10-1000 microg/mL). The lowest garlic concentration (10 microg/mL) increased the normal explant production of IL-10 by 29.2% (12.2, 57.5%; p<0.01) while inhibiting the production of IL-6 by 23.5% (8.9, 32.5%; p<0.01) (normal explants) and TNFalpha by 19.4% (4.5, 35.3%; p<0.05) (preeclamptic explants). Garlic resulted in an increase in IL-10 production at lower doses (normal explants only) and inhibition of the production of IL-10 at higher doses (normal and preeclamptic explants). Garlic also resulted in a dose-dependent reduction of IL-6 and TNFalpha. Initially there was no change in sTRAIL production; however, at the highest garlic concentrations there was a significant increase in production. We thus conclude that garlic may have an immunomodulatory effect on normal and preeclamptic placentas.
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PMID:Garlic increases IL-10 and inhibits TNFalpha and IL-6 production in endotoxin-stimulated human placental explants. 1622 32

Renal involvement is common in multiple myeloma and implies much worse prognosis. Most of the kidney disorders associated with myeloma are caused by the excess production of monoclonal light chains, and renal involvement is almost always accompanied by light chain proteinuria. Light chains have variable effects on the kidney; some are more toxic than others and different light chains affect different structures in the kidney. In normal quantities light chains are filtered relatively unhindered in the glomerulus and endocytosed by the proximal tubule cells through the tandem endocytic receptors megalin/cubilin and targeted to degradative sites. Proximal tubule injury is the most common mode of renal involvement and it can manifest in a variety of ways. When light chains are overproduced the proximal tubular endocytic process is overloaded and cell stress responses that include phosphorylation of MAPKs, prominently, p38 MAPK, and nuclear transcription factors NF-kappaB, AP-1 are activated resulting in production of inflammatory and proinflammatory cytokines, TNF-alpha, interleukin-6, 8, and monocyte chemo-attractant protein-1. In early stages of myeloma, light chain nephrotoxicity often presents with proximal tubular functional abnormalities, such as Fanconi syndrome. These proximal tubule alterations often progress to a severe tubulointerstitial kidney disease, the most common type of kidney involvement responsible for endstage renal failure seen in myeloma patients.
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PMID:Proximal tubular injury in myeloma. 1707 25

Hyperaldosteronism is associated with hypertension, cardiovascular fibrosis, and electrolyte disturbances, including hypomagnesemia. Mechanisms underlying aldosterone-mediated Mg(2+) changes are unclear, but the novel Mg(2+) transporters TRPM6 and TRPM7 may be important. We examined whether aldosterone influences renal TRPM6/7 and the TRPM7 downstream target annexin-1 and tested the hypothesis that Mg(2+) administration ameliorates aldosterone-induced cardiovascular and renal injury and prevents aldosterone-associated hypertension. C57B6 mice were studied (12 weeks, n=8 to 9/group); (1) control group (0.2% dietary Mg(2+)), (2) Mg(2+) group (0.75% dietary Mg(2+)), (3) aldosterone group (Aldo, 400 microg/kg/min and 0.9% NaCl drinking water), and (4) Aldo+Mg(2+) group. Blood pressure was unaltered by aldosterone and was similar in all groups throughout the experiment. Serum Na(+) was increased and serum K(+) and Mg(2+) decreased in the Aldo group. Aldo mice had hypomagnesuria and proteinuria, and renal, cardiac, and aortic fibrosis, which were normalized by Mg(2+) supplementation. Renal and cardiovascular expression of interleukin-6, VCAM1 and COX2 was increased in the Aldo group. Magnesium attenuated renal and cardiac interleukin-6 content and decreased renal VCAM1 and cardiac COX2 expression (P<0.05). Aldosterone decreased expression of renal TRPM7 and the downstream target annexin-1 (P<0.05) without effect on TRPM6. Whereas Mg(2+) increased mRNA expression of TRPM6 and TRPM7, it had no effect on TRPM7 and annexin-1 protein content. Our data demonstrate that aldosterone mediates blood pressure-independent renal and cardiovascular fibrosis and inflammation through Mg(2+)-sensitive pathways. We suggest that altered Mg(2+) metabolism in hyperaldosteronism may relate to TRPM7 downregulation and that Mg(2+) protects against cardiovascular and renal damaging actions of aldosterone.
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PMID:Downregulation of renal TRPM7 and increased inflammation and fibrosis in aldosterone-infused mice: effects of magnesium. 1826 39

Castleman's disease is a rare atypical lymphoproliferative disorder. Renal manifestations, such as proteinuria, hematuria, and renal dysfunction, are common in Castleman's disease; however, a nephrotic syndrome rarely occurs. We have encountered an unusual case of Castleman's disease of the plasma cell type characterized by nephrotic syndrome because of glomerulopathy mimicking membranoproliferative glomerulonephritis. Our patient showed higher levels of circulating cytokines (interleukin-6/vascular endothelial cell-derived growth factor), the glomerular lesions not associated with immunocomplex deposition, and the resolution of nephrotic syndrome after successful corticosteroids therapy resulting in a decline in cytokines levels, thereby implicating a cytokine-induced glomerular cell injury/activation as a possible cause of the glomerular pathological changes in this case.
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PMID:A case of Castleman's disease complicated with nephrotic syndrome due to glomerulopathy mimicking membranoproliferative glomerulonephritis. 1855 83

The present study was conducted to compare the renal and vascular protective effects of telmisartan and amlodipine in untreated hypertensive chronic kidney disease (CKD) patients with moderate renal insufficiency. Thirty hypertensive CKD patients were randomly assigned to receive telmisartan 40 mg (n = 15) or amlodipine 5 mg (n = 15) once daily for 12 months. Changes in blood pressure, serum creatinine, 24-h creatinine clearance (Ccr), proteinuria, brachial-ankle pulse wave velocity (baPWV), intima-media thickness (IMT), plasma interleukin-6 (IL-6), plasma matrix metalloproteinase (MMP)-9 and lipid profiles were monitored in all patients. Before treatment, there were no significant differences in these parameters between the telmisartan and amlodipine groups. Over the 12 month observation period, blood pressure decreased equally in both groups. However, serum creatinine, proteinuria, baPWV, IMT, plasma levels of IL-6 and MMP-9 and total cholesterol decreased and 24-h Ccr increased more strikingly in the telmisartan group than the amlodipine group. These data suggest that telmisartan is more effective than amlodipine for protecting renovascular functions, and potentially for ameliorating atherosclerosis, in hypertensive CKD patients with moderate renal insufficiency.
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PMID:Comparison of renal and vascular protective effects between telmisartan and amlodipine in hypertensive patients with chronic kidney disease with mild renal insufficiency. 1913 8

Hyperlipidemia has been demonstrated to be associated with renal disease, yet the mechanism of renal injury is still poorly understood. Inflammation that occurs with the hyperlipidemia has been considered to play an important role in development of glomerular injury. In the present study, we investigated the role of interleukin-6 (IL-6), a key inflammatory molecule, on renal injury in apolipoprotein E-deficient (ApoE(-/-)) mice with severe hypercholesterolemia. The 6-wk-old mice were fed a high-fat diet and administered weekly rat anti-IL-6 receptor monoclonal antibody (MR16-1), control rat IgG, or saline for a total of 4 wk. We examined histopathological changes in the kidney and urinary excretion of protein and albumin. Saline- and IgG-treated mice showed remarkable proteinuria at 10 wk of age, whereas MR16-1-treated mice exhibited significantly lower levels. Renal histopathology of saline- and IgG-treated mice revealed striking lipid deposits and foam cells in the glomerular tuft, juxtaglomerular area, and arteriolar wall along with range of mesangial cell proliferation and matrix expansion. Notably, the severity of lipid deposits and mesangial cell proliferation were significantly reduced in MR16-1-treated mice. Immunohistochemistry demonstrated that mesangial IL-6 expression was dramatically reduced in MR16-1-treated mice compared with IgG-treated mice. Blocking the IL-6 receptor prevented progression of proteinuria and renal lipid deposit, as well as the mesangial cell proliferation associated with severe hyperlipoproteinemia. These results clearly demonstrate that IL-6 plays an essential role in the pathogenesis of hyperlipidemia-induced glomerular injury in ApoE(-/-) mice and suggests the usefulness of anti-IL-6 receptor antibody in treatments for hyperlipidemia-induced organ damage.
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PMID:Effect of interleukin-6 receptor blockage on renal injury in apolipoprotein E-deficient mice. 1957 Aug 77


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