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)

Multiple cases of IgA nephropathy (IgAN) may occur in families; we compared their prognosis to sporadic cases of this disease. We isolated macromolecular IgA1 from 60 patients with familial IgAN, 91 of their asymptomatic relatives, 43 patients with sporadic IgAN (SpIgAN), 90 of their asymptomatic relatives, and 43 healthy subjects. Compared with SpIgAN patients, those with multiplex familial IgAN (MpIgAN) had more advanced renal histopathology and more galactose-deficient macromolecular IgA1 in their serum. Further, when we tested the effects of the macromolecular IgA1 on human mesangial cells in culture, we found that the macromolecular IgA1 taken from familial clusters had enhanced binding to mesangial cells and caused increased expression of interleukin-6, tumor necrosis factor-alpha, and monocyte chemotactic peptide-1. The macromolecular IgA1 isolated from asymptomatic relatives caused increased cytokine expression in the mesangial cells when derived from MpIgAN compared with SpIgAN or healthy controls. While these studies suggest that macromolecular IgA1 isolated from patients with MpIgAN is more pathogenic than that from patients with SpIgAN, long term follow-up will be needed to clarify the risk in asymptomatic relatives of the patients with multiplex familial disease.
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PMID:Macromolecular IgA1 taken from patients with familial IgA nephropathy or their asymptomatic relatives have higher reactivity to mesangial cells in vitro. 1934 88

A 35-year-old Japanese man developed systemic lymphadenopathy during the course of immunosuppressive therapy for IgA nephropathy associated with cutaneous nodules, polyclonal hypergammaglobulinemia, and persistent increased serum C-reactive protein of unknown cause. Lymph node examination showed the plasmacytic type of Castleman disease (CD). A skin biopsy showed specific pathologic findings of CD cutaneous involvement. Considering the involvement of interleukin-6 in CD, we treated the patient with humanized anti-interleukin-6 receptor antibody. Thereafter, his symptoms and abnormal laboratory findings were improved. Cutaneous CD has rarely been described in Asian population, and renal complications in CD are uncommon and heterogeneous. To our knowledge, this is the first case of IgA nephropathy associated with multicentric CD with cutaneous involvement.
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PMID:IgA nephropathy associated with Castleman disease with cutaneous involvement. 2033 84

Tubulointerstitial infiltration of immunocompetent cells is often associated with a more rapid progression in IgA nephropathy (IgAN). Using an in vitro Transwell coculture system, we examined the chemotactic response of peripheral blood mononuclear cells to proximal tubular epithelial cells (PTEC) following activation by conditioned medium prepared from mesangial cells cultured with macromolecular IgA1 from 60 patients with multiplex familial IgAN (MpIgAN) and 91 of their asymptomatic relatives; 43 patients with sporadic IgAN (SpIgAN) and 90 of their asymptomatic relatives; and 43 healthy subjects. Compared with SpIgAN patients, PTEC activated by conditioned medium from patients with MpIgAN had elevated gene expression of a spectrum of C-C, C-X-C chemokines and proinflammatory cytokines, with prominent expressions of interleukin-6, interleukin-8, and tumor necrosis factor-alpha. In response to conditioned medium from patients with familial IgAN, there was a significant increase in chemotaxis of CD45+ cells, CD3+, CD4+, CD8+, CD20+ lymphocytes, and monocytes with CD25 expression. Our findings suggest that compared with SpIgAN patients, macromolecular IgA1 taken from MpIgAN patients is more pathogenic to cultured PTEC through a glomerulotubular interaction. A long-term follow-up is needed to better define the prognostic course for familial IgAN and to clarify the risk of developing IgAN in initially asymptomatic relatives from a multiplex IgAN family.
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PMID:In vitro enhanced chemotaxis of CD25+ mononuclear cells in patients with familial IgAN through glomerulotubular interactions. 2048 97

Interleukin-6 (IL-6) is a pleiotropic cytokine that not only regulates the immune and inflammatory response but also affects hematopoiesis, metabolism, and organ development. IL-6 can simultaneously elicit distinct or even contradictory physiopathological processes, which is likely discriminated by the cascades of signaling pathway, termed classic and trans-signaling. Besides playing several important physiological roles, dysregulated IL-6 has been demonstrated to underlie a number of autoimmune and inflammatory diseases, metabolic abnormalities, and malignancies. This review provides an overview of basic concept of IL-6 signaling pathway as well as the interplay between IL-6 and renal-resident cells, including podocytes, mesangial cells, endothelial cells, and tubular epithelial cells. Additionally, we summarize the roles of IL-6 in several renal diseases, such as IgA nephropathy, lupus nephritis, diabetic nephropathy, acute kidney injury, and chronic kidney disease.
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PMID:Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. 2848 49

Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member 6b (TNFRSF6B), was recently identified as a novel biomarker for predicting progression of kidney diseases with potential immune modulation. The purpose of this review is to discuss the current evidence related to DcR3 in kidney diseases and to compare the differences between human and animal studies both in vivo and in vitro. High serum DcR3 predicts the occurrence of peritonitis in patients receiving chronic peritoneal dialysis and is positively correlated with inflammatory markers such as interleukin-6, high-sensitivity C-reactive protein, and adhesion molecules in patients on maintenance hemodialysis (HD). Higher serum DcR3 levels not only independently predict cardiovascular and all-cause mortality in HD patients but also identify older adults on HD at risk of protein-energy wasting in combination with a low geriatric nutritional risk index. Recently, renal tubular epithelial cells (RTECs) expressing DcR3 have also been used to predict progression of chronic kidney disease. Expression of DcR3 was correlated with a 2-fold increase in serum creatinine or failure of kidney allograft. DcR3 could protect renal myofibroblasts against Fas-induced apoptosis and subsequently lead to renal fibrosis. Locally expressed DcR3 in the RTECs may suppress the FasL-Fas-mediated apoptosis of T cells, resulting in an accumulation of allo-reactive T cells. In addition to traditional biological functions, recombinant DcR3.Fc and cytomegalovirus promoter-driven human DcR3 plasmid are able to modulate the activation and differentiation of dendritic cells and macrophages via "non-decoy" action. Both progressive IgA nephropathy and autoimmune crescentic glomerulonephritis in mice can be suppressed after hydrodynamics-based gene delivery of DcR3 plasmid. DcR3-mediated effects in vitro could be surveyed via over-expressing DcR3 or addition of recombinant DcR3.Fc, and CD68-driven DcR3 transgenic mice are suitable for investigating systemic effect in vivo. Inhibition of DcR3 expression in human may be a promising approach for pathomechanism.
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PMID:Role of prognostic biomarker decoy receptor 3 and immunomodulation in kidney diseases. 3135 60

Galactose-deficient immunoglobulin A1 (Gd-IgA1) was recently identified as a critical effector molecule in the pathogenesis of IgA nephropathy (IgAN). Gd-IgA1 is produced by the mucosal immune system. IgAN is thought to develop because of the deposition of a circulating immune-complex containing Gd-IgA1 in the kidney. Multicentric Castleman's disease (MCD) is a rare non-neoplastic lymphoproliferative disorder. As an etiology model, hypercytokinemia, including increased levels of interleukin-6, is the primary pathogenesis of many MCD cases. Here, we present two cases of mesangial proliferative glomerulonephritis with MCD. According to renal biopsy findings, one was diagnosed with non-IgAN and the other with IgAN. Surprisingly, in both cases, Gd-IgA1 was produced by plasma cells in the lymph nodes, suggesting that Gd-IgA1 production alone does not cause IgAN; rather, it may be produced without induction by mucosal immunity. Our findings demonstrate the diversity of the development of IgAN and help to reconsider the onset mechanism of IgAN.
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PMID:Case report on mesangial proliferative glomerulonephritis with multicentric Castleman's disease: Approach to the onset mechanism of immunoglobulin A nephropathy. 3197 58


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