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)

Glomerulonephritis (GN) results in proliferation of mesangial cells (MC), infiltration of inflammatory cells, and accumulation of extracellular matrix (ECM) proteins in the mesangium. Locally secreted cytokines may stimulate MC growth or the secretion of inflammatory mediators by MC. Interleukin-6 (IL-6) may be an autocrine cofactor in the pathogenesis of mesangioproliferative GN. We studied the regulation of IL-6 secretion by MC in response to MC-derived cytokines and ECM proteins. IL-6 secretion is stimulated in a dose-dependent manner by IL-1 alpha, TNF-alpha, and PDGF. Constitutive and LPS-induced release of IL-6 by MCs is reduced on collagen type I (coll I) compared-with uncoated surfaces. IL-6 release on collagen type IV (coll IV), however, is enhanced. In addition, MC on coll I exhibit a sixfold higher growth rate than cells on uncoated surfaces. The reduction of cytokine secretion in parallel with the stimulation of MC growth by coll I suggests that exposure to coll I may result in a change from secretory to proliferative phenotype in vitro.
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PMID:Mesangial cell-matrix interactions. Effects on mesangial cell growth and cytokine secretion. 132 20

Interleukin-6 (IL-6) plays a key role in inflammatory and immune responses in the host. In the present study, the IL-6 activity in urine from patients with various renal diseases was examined to elucidate the pathological and clinical significance of urinary IL-6. In patients with mesangial proliferative glomerulonephritis (mes-PGN) including, IgA nephropathy, the urinary IL-6 activity tended to increase with the progression of mesangial hypercellularity. In four patients with IgA nephropathy, urinary IL-6 activity increased markedly but transiently during episodes of acute exacerbation associated with upper respiratory tract infection. In addition, it was demonstrated that urine from patients with other types of PGN such as poststreptococcal acute glomerulonephritis and membrano-proliferative glomerulonephritis contained large quantities of IL-6. However, the levels of urinary IL-6 activity were almost within the normal range in non-proliferative glomerular diseases such as membranous nephropathy, minimal change nephrotic syndrome and lupus nephritis (WHO class I and V), non-glomerular bleeding and orthostatic proteinuria. It should be noted that a marked increase in urinary IL-6 was often observed in the patients with urinary tract infection. These results indicated that IL-6 in urine might be derived from various types of cells participating in inflammatory reactions not only in the renal parenchyma but also in the urinary tract.
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PMID:Detection and clinical usefulness of urinary interleukin-6 in the diseases of the kidney and the urinary tract. 142 4

Interleukin-6, IL-6, is a pleiotropic cytokine which plays a central role in defense mechanisms, including the immune response, acute phase reaction and hematopoiesis. Abnormal expression of the IL-6 gene has been suggested to be involved in the pathogenesis of a variety of diseases, especially rheumatoid arthritis, Castleman's disease, mesangial proliferative glomerulonephritis, multiple myeloma and Kaposi's sarcoma. In the case of multiple myeloma and Kaposi's sarcoma, the existence of an IL-6-IL-6 receptor autocrine loop has been implicated in the oncogenesis process. On the other hand, IL-6 has a potent anti-tumor activity against certain types of tumors. This anti-tumor effect is mediated by in vivo induction of tumor specific cytotoxic T cells and in part by a growth inhibitory activity of IL-6.
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PMID:The evidence for interleukin-6 as an autocrine growth factor in malignancy. 164 91

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase reactions, and hematopoiesis. Its receptor system consists of two molecules: a ligand-binding 80-kDa molecule and a non-ligand-binding signal transducer, gp 130, both of which were found to belong to the cytokine receptor family. Deregulated IL-6 gene expression has been implicated as being involved in the pathogenesis of a number of diseases, especially autoimmune diseases and plasma cell neoplasias. In fact, IL-6 transgenic C57BL/6 mice showed a massive polyclonal plasmacytosis with production of autoantibodies and mesangial proliferative glomerulonephritis, indicating that IL-6 plays a critical role in the development of plasma cell abnormalities and glomerulonephritis.
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PMID:Interleukin-6 and its relation to inflammation and disease. 172 89

Interleukin-6 (IL-6) is a multifunctional cytokine exerting a wide variety of biologic responses, including cell proliferation. Recently, IL-6 has been known to play a role in the pathogenesis of mesangial proliferative glomerulonephritis. IL-6 is now recognized as an autocrine growth factor for glomerular mesangial cells, and various inflammatory mediators have been shown to promote IL-6 release from mesangial cells. However, little is known about the noninflammatory stimuli of IL-6 release from mesangial cells. In this study, it was hypothesized that angiotensin II (AngII) is one of the noninflammatory mediators of IL-6 release in mesangial cells, and the effects of AngII on IL-6 release and mRNA expression in cultured mouse mesangial cells (CMMC) were investigated. It was demonstrated that AngII (10(-7) M or higher) caused IL-6 release and mRNA accumulation in CMMC. IL-6 release was detected at 4 h and reached a plateau at 8 h after the addition of AngII, whereas IL-6 mRNA expression peaked at 4 h. The effects of AngII on IL-6 release and gene expression were completely blocked by the AngII receptor type 1 (AT1 receptor) antagonist CV-11974. AngII and IL-6 were both shown to stimulate DNA synthesis in CMMC, and the blockade of IL-6 signaling with anti-IL-6 receptor antibody abolished the enhanced DNA synthesis induced by AngII. These results raise a possibility that the growth-promoting effect of AngII on mesangial cells is at least partially mediated by IL-6 released from mesangial cells.
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PMID:Angiotensin II stimulates interleukin-6 release from cultured mouse mesangial cells. 757 76

CD16, a low affinity receptor for IgG, was found on cultured human glomerular mesangial cells (GMC) by Western blot analysis, cell ELISA and in situ hybridization. To characterize the molecule in more detail, reverse polymerase chain reaction was performed and the PCR products were analyzed. From sequence analysis and from hybridization experiments with oligonucleotides specific for either the transmembrane form or the glycosylphosphatidylinositol anchored form it was found that GMC-CD16 was similar to NK-CD16. This indicates that GMC express the transmembrane form of CD16. Comparison between nonstimulated GMC and GMC stimulated by aggregated gammaglobulin revealed no qualitative or quantitative difference in the expression of CD16. Incubation of GMC with aggregated gammaglobulin or with monoclonal antibodies to CD16 was followed by a time and dose dependent release of interleukin-6, suggesting that signals were transmitted by CD16. The occupancy of CD16 by immune complexes that may be deposited in various forms of glomerulonephritis might contribute to the perpetuation of inflammatory processes in the kidney.
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PMID:Human glomerular mesangial cells express CD16 and may be stimulated via this receptor. 770 21

Intrinsic glomerular cells, especially mesangial cells, are considered to be actively involved in the pathogenesis of glomerulonephritis (GN), but the precise mechanism(s) remains elusive. We have previously demonstrated that nephritogenic IgA immune complex can stimulate human mesangial cells (HMCs) to increase their production of interleukin-1 (IL-1) and interleukin-6 (IL-6). In order to evaluate the roles of cytokines such as IL-1 and/or IL-6 and mesangial cells as mediators of renal injury in GN, we have now examined the changes of HMCs and their secreted products in vitro, after stimulation with various concentrations of IL-1 and IL-6. Cytokine-activated HMCs showed the following changes: (1) increased cell size, with intracytoplasmic vacuoles, dilated endoplasmic reticulum, increased free ribosomes and polysomes, and mitochondrial swelling; (2) increased cell proliferation, reflected in thymidine incorporation and an increased proportion of S and G2/M phase cells by cell cycle analysis; (3) enhancement of IL-6 mRNA expression in HMCs with stimulation of IL-6 alone or IL-1 plus IL-6; and (4) release of large amounts of platelet activating factor (PAF), thromboxane B2 (TxB2), and superoxide anion. Taken together, these results strongly suggest that mesangial cell proliferation and increased production of immune/chemical mediators and superoxide anion can be directly induced by IL-1 plus IL-6. These changes may lead to ongoing renal injury.
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PMID:In vitro effects of interleukins on human mesangial cells: implications for glomerulonephritis. 774

Infiltration of leukocytes and mononuclear cells into the glomeruli is an early pathological finding in human and experimental glomerulonephritis. However, the cellular and molecular basis for cell infiltration into the glomeruli is not yet completely understood. In addition, there is little information on the expression of intercellular adhesion molecule-1 (ICAM-1) on glomerular cells. In the present study, we investigated the expression of ICAM-1 on cultured bovine glomerular endothelial cells (GEN) and its regulation by the pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and lipopolysaccharide (LPS). Immunocytochemical staining showed that ICAM-1 molecules were constitutively expressed on the surface of GEN. In flow cytometric and ELISA analyses, ICAM-1 molecule expression on GEN was significantly upregulated by IL-1 beta, MCP-1 and LPS in a dose-dependent manner, but not by IL-6. LPS was the most potent inducer of ICAM-1 molecule expression on GEN. The effects of IL-1 beta, MCP-1 and LPS were observed as early as 4 h and reached a maximal level by 18 h. These results suggest that ICAM-1 on GEN can participate in the infiltration of mononuclear cells into glomeruli in human and experimental glomerulonephritis.
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PMID:Expression of intercellular adhesion molecule-1 on cultured glomerular endothelial cells by pro-inflammatory cytokines and lipopolysaccharide. 775

Aleutian mink disease (AD) is a naturally occurring persistent virus infection of mink caused by the Aleutian mink disease parvovirus (ADV). The classical form of AD, which occurs in adult mink, is notable for high titers of antiviral antibodies, hypergammaglobulinemia, plasmacytosis, and immune complex disease. In addition, there is a progressive renal disease characterized by mesangial proliferative glomerulonephritis and severe interstitial nephritis. Development of AD depends on both host and viral factors, and mink of certain genotypes fail to develop progressive disease when inoculated with low-virulence strains of virus. In newborn mink kits, ADV causes a fatal, acute interstitial pneumonitis associated with permissive viral replication in alveolar type 2 cells, but treatment of newborn kits with anti-viral antibody aborts the acute disease and converts into one resembling the persistent infection observed in adults. In infected adult mink, ADV is sequestered as immune complexes in lymphoid organs, but actual viral replication is restricted at the level of the individual cell and can be detected in only a small population of macrophages and follicular dendritic cells. ADV infection of mink primary macrophages and the human macrophage cell line U937 is antibody dependent and leads to the production of the cytokine interleukin-6. Furthermore, levels of interleukin-6 are increased in lymph node culture supernatants from infected mink. Chronic production of interleukin-6 may promote development of the immune disorder characteristic of AD.
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PMID:Aleutian mink disease: puzzles and paradigms. 788 16

In crescentic glomerulonephritis, crescent formation involves the active participation of glomerular epithelial cells (GEC) and macrophages recruited to the glomerulus during the evolution of the disease. Cytokines derived from macrophages may affect many functions of GEC. In this study, we found that interleukin-1 beta (IL-1 beta) inhibited GEC growth (DNA synthesis and cell number) in vitro in a dose- and time-dependent manner. This effect was not mediated by tumor growth factor beta (TGF beta) which is a potent inhibitor of GEC growth in vitro. Treatment of GEC with various concentrations of IL-1 beta induced morphologic changes consisting in the loss of their cobblestone shape and acquisition of a fibroblast-like appearance. Moreover, IL-1 beta was shown to stimulate the expression of interleukin-6 (IL-6) by GEC. The increase in IL-6 secretion by GEC treated with IL-1 beta was observed at both the protein and mRNA levels. IL-1 beta also affected the metabolism of laminin in cultured GEC, inducing a dose-dependent increase in laminin production in culture supernatants harvested from GEC. Finally, we investigated the expression of MHC class II antigens and intercellular adhesion molecule-1 (ICAM-1) in GEC, and found that unstimulated GEC are negative for MHC class II antigens, as detected by flow cytometry. In contrast to the induction of effector functions, expression of MHC class II antigens stringently required interferon-gamma. IL-1 beta did not induce MHC class I antigen expression. The regulation of ICAM-1 expression in that unstimulated GEC expressed ICAM-1, and this expression was upregulated by IL-1 beta. We conclude that IL-1 beta alters many functions of GEC, and these changes may be involved in the initiation and amplification of glomerular injury.
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PMID:Interleukin-1-beta activation of cultured glomerular epithelial cells. 792 73


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