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)

Severe combined immunodeficiency (SCID) mice were engrafted with rheumatoid arthritis (RA) synovium and evaluated to determine whether RA synovial morphology and function were maintained in the RA-SCID grafts. The four major components of RA synovitis, inflammation, immune reactivity, angiogenesis, and synovial hyperplasia persisted in RA-SCID grafts for 12 weeks. Retention of chronic inflammatory infiltrates was demonstrated by histological evaluation and by immunohistology for CD3, CD20, and CD68. Staining for CD68 also revealed that the grafts had undergone reorganization of the tissue, possibly as a result of fibroblast hyperplasia. Immune and inflammatory components were confirmed by the detection of human immunoglobulins and human interleukin-6 in serum samples obtained from grafted animals. Human blood vessels were detected by dense expression of CD31. Small vessels persistently expressed the vitronectin receptor, alpha v beta 3, a marker of angiogenesis. All vessels expressed VAP-1, a marker of activated endothelial cells. Finally, the grafts retained the ability to support immigration by human leukocytes, as demonstrated by the functional capacity to recruit adoptively transferred 5- (and -6)-carboxyfluorescein diacetate succinimidyl ester-labeled T cells. T cells entering the RA-SCID grafts became activated and produced interferon-gamma, as detected by reverse transcriptase-polymerase chain reaction analysis. These studies demonstrate that the RA-SCID model maintains many of the phenotypic and functional features of the inflamed RA synovium.
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PMID:Inflammation, immune reactivity, and angiogenesis in a severe combined immunodeficiency model of rheumatoid arthritis. 1178 29

Little is known regarding the timing of immune ontogeny and effector function in fetal humans and nonhuman primates. We studied the organization of lymphocyte and antigen-presenting cell populations in developing lymphoid tissues of rhesus monkey fetuses during the second and third trimesters (65 to 145 days of gestation; term = 165 days). Immunoglobulin-secreting and cytokine-secreting cells were detected at day 80. The thymus, spleen, lymph nodes, and intestinal mucosa were examined for cells expressing CD3, CD5, CD20, CD68, p55, and HLA-DR. In the spleens of 65-day-old fetuses (early second trimester), the overwhelming majority of total lymphocytes were CD5(+) CD20(+) B-1 cells. The remaining lymphocytes were CD3(+) T cells. By day 80, splenic B and T cells were equal in number. Intraepithelial CD3(+) CD5(-) T cells and lamina propria CD20(+) CD5(+) B cells were present in the intestines of 65-day-old fetuses. By day 80, numerous CD20(+) CD5(+) B cells were present in the jejunums and colons and early lymphocyte aggregate formation was evident. The spleens of 80- to 145-day-old fetuses contained immunoglobulin M (IgM)-secreting cells, while IgA-, IgG-, interleukin-6-, and gamma interferon-secreting cells were numerous in the spleens and colons. Thus, by the second trimester, the lymphoid tissues of the rhesus monkey fetus have a complete repertoire of properly organized antigen-presenting cells, T cells, and B cells.
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PMID:Functional and morphological development of lymphoid tissues and immune regulatory and effector function in rhesus monkeys: cytokine-secreting cells, immunoglobulin-secreting cells, and CD5(+) B-1 cells appear early in fetal development. 1252 52

Interleukin-6 (IL-6) is a multifunctional cytokine with a growth promoting role in cancers. In an attempt to evaluate the prognostic significance of IL-6, we have studied the localization of this cytokine by immunohistochemical methods in normal, premalignant, and invasive cervical cancers. We stained frozen sections with a monoclonal antibody specific for human IL-6 and demonstrated that tumor cells show positivity with high intensity and stromal cells with moderate intensity. T cells and macrophages, components of the stroma that secrete IL-6, were also looked at. While T cells showed a weak positive correlation, CD68-positive macrophages showed significant positive correlation (P < 0.05) with IL-6 positivity in stroma. The patients were followed up for 40 months after treatment with standard radiotherapy regimen and showed residual tumor where pretreatment IL-6 levels were high. Our results suggest its possible candidature as a prognostic indicator of cervical cancer.
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PMID:A prognostic insight on in vivo expression of interleukin-6 in uterine cervical cancer. 1280 Dec 65

Because of variations in the morphology and function of microglial cells, it has often been claimed that microglial cells should be classified into two or more subtypes. However, such subtypes have not fully been characterized. In the present study, we isolated microglial cells expressing microglia-markers CD11b and CD68 from rat mixed glial cultures on the fifth and on the thirteenth days in vitro (DIV 5 and 13) and demonstrate that these two populations of microglial cells have distinct morphology and function. Microglial cells isolated on DIV 5, which we have termed immature cells, are characterized by the presence of large somata, large peroxidase- and alkaline phosphatase-positive granules, and high proliferative activity and suppressed responsiveness to lipopolysaccharide (LPS). In contrast, the microglial cells isolated on DIV 13, which we have termed mature cells, are devoid of granules, appear to be in a state of cell cycle arrest, and respond to LPS by the induction of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin-6. Isolated immature cells maintained in pure culture failed to express iNOS in response to LPS. However, if these cells were cultured on astrocyte-derived extracellular matrix (AsECM) or pure laminin, the cells exhibited an induction of iNOS in response to LPS. AsECM and laminin were also able to induce a state of cell cycle arrest in cultured isolated immature cells. Thus, classification into two types of microglial cells is possible, but both types are in the same cell lineage, because the immature cells can differentiate into mature microglial cells in the presence of laminin or AsECM. Therefore, "microglioblasts" may be the appropriate term for the immature cells.
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PMID:Two populations of microglial cells isolated from rat primary mixed glial cultures. 1281 5

Cytokines and chemokines including interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) are secreted in response to major abdominal operations. The aim of this study was to identify the peritoneal cells that produce IL-6 and MCP-1. Samples of peritoneal tissue were taken from patients at the beginning and end of major abdominal operations. The samples were incubated in culture medium on microtitre plates for 5 h. The concentrations of IL-6 and MCP-1 were measured in culture supernatants by enzyme-linked immunosorbent assay (ELISA). In paraffin sections, cells that expressed IL-6 or MCP-1 were identified by combined in situ hybridization and immunohistochemistry. Antibodies against CD68, CD34, actin, and calretinin were included in these experiments. The median production of IL-6 increased significantly from 6256 pg/ml at the start of the operation to 20,000 pg/ml at the end. Production of MCP-1 rose from 7700 pg/ml to 11,820 pg/ml. IL-6 mRNA was mainly confined to endothelial cells. MCP-1 was expressed by a broader range of cells, consisting of actin-positive smooth muscle cells and endothelial cells, fibroblast-like cells, as well as occasional macrophages and mesothelial cells. Peritoneal endothelial cells contribute to the transient increase in concentrations of IL-6 in the circulation after surgical trauma. Recruitment of monocytes to the site of the trauma seems to be mainly effected by actin-positive smooth muscle cells and endothelial cells.
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PMID:Expression of interleukin-6 and monocyte chemoattractant protein-1 by peritoneal sub-mesothelial cells during abdominal operations. 1469 19

Binding of ligands to the receptor for advanced glycation endproducts (RAGE) results in activation of the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) and subsequent expression of NF-kappaB-regulated cytokines. In order to determine whether engagement of RAGE contributes to the pathogenesis of vasculitic neuropathy, we studied the presence of the RAGE ligand N(epsilon)-(carboxymethyl)lysine (CML), the receptor itself, NF-kappaB, and interleukin-6 (IL-6) in sural nerve biopsies of 12 patients with vasculitic neuropathies and 12 controls. In the patients, CML, RAGE, NF-kappaB, and IL-6 were localized in mononuclear cells, epineurial and endoneurial vessels and the perineurium. CML, RAGE, NF-kappaB, and IL-6 were expressed by CD4(+), CD8(+), and CD68(+) cells invading the nerves. Controls showed only weak staining. These data suggest that the RAGE pathway plays a critical proinflammatory role in vasculitic neuropathy.
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PMID:Receptor for advanced glycation endproduct (RAGE)-mediated nuclear factor-kappaB activation in vasculitic neuropathy. 1517 Jun 18

To examine the role of adipose-resident macrophages in insulin resistance, we examined the gene expression of CD68, a macrophage marker, along with macrophage chemoattractant protein-1 (MCP-1) in human subcutaneous adipose tissue using real-time RT-PCR. Both CD68 and MCP-1 mRNAs were expressed in human adipose tissue, primarily in the stromal vascular fraction. When measured in the adipose tissue from subjects with normal glucose tolerance, covering a wide range of BMI (21-51 kg/m2) and insulin sensitivity (S(I)) (0.6-8.0 x 10(-4)min(-1).microU(-1).ml(-1)), CD68 mRNA abundance, which correlated with the number of CD68-positive cells by immunohistochemistry, tended to increase with BMI but was not statistically significant. However, there was a significant inverse relation between CD68 mRNA and S(I) (r=-0.55, P=0.02). In addition, there was a strong positive relationship among adipose tissue CD68 mRNA, tumor necrosis factor-alpha (TNF-alpha) secretion in vitro (r=0.79, P<0.005), and plasma interleukin-6 (r=0.67, P < 0.005). To determine whether improving S(I) in subjects with impaired glucose tolerance (IGT) was associated with decreased CD68 expression, IGT subjects were treated for 10 weeks with pioglitazone or metformin. Pioglitazone increased S(I) by 60% and in the same subjects reduced both CD68 and MCP-1 mRNAs by >50%. Furthermore, pioglitazone resulted in a reduction in the number of CD68-positive cells in adipose tissue and reduced plasma TNF-alpha. Metformin had no effect on any of these measures. Thus, treatment with pioglitazone reduces expression of CD68 and MCP-1 in adipose tissue, apparently by reducing macrophage numbers, resulting in reduced inflammatory cytokine production and improvement in S(I).
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PMID:Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. 1604 95

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

Synovial macrophages play an outstanding role in many rheumatic diseases. However, traditional serum-containing tissue-culture techniques hamper in vitro studies due to fibroblast activation not found in vivo. The objective of this study was to examine dissociated synovial cells in a macrophage-selective, serum-free tissue-culture medium. Osteoarthritis synovial tissue (n=11) was cultured in Iscove's Modified Dulbecco's Medium (IMDM) with 10% fetal bovine serum (FBS) and compared to a serum-free, insulin-supplemented medium. After 9-11 and 19-21 days in vitro, immunohistochemistry was performed for macrophage/lymphocyte markers and cell division. Cytokine profiles were determined by RT-PCR. In serum, cells with a bipolar morphology rapidly proliferated. Respectively, 14.34+/-12.94% and 13.25+/-12.66% expressed CD68 and HLA-DR. These markers further decreased after one passage. In serum-free medium, proliferation was infrequent, and cells with diverse morphologies expressed 83.10+/-6.80% and 55.03+/-6.88% CD68 and HLA-DR respectively. CD14 was rare, and lymphocytes were missing. Both cultures expressed interleukin-6 and interleukin-8. This novel serum-free method permits the culture of distinct CD68/HLA-DR associated phenotypes.
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PMID:Macrophage-like synoviocytes display phenotypic polymorphisms in a serum-free tissue-culture medium. 1636 55

Recent Parkinson's disease research has focused on understanding the function of the cytosolic protein, alpha-synuclein, and its contribution to disease mechanisms. Within neurons, alpha-synuclein is hypothesized to have a role in regulating synaptic plasticity, vesicle release, and trafficking. In contrast, glial-expressed alpha-synuclein remains poorly described. Here, we examine the consequence of a loss of alpha-synuclein expression on microglial activation. Using a postnatal brain-derived culture system, we defined the phenotype of microglia from wild-type and knock-out alpha-synuclein mice (Scna-/-). Scna-/- microglia displayed a basally increased reactive phenotype compared with the wild-type cells and an exacerbated reactive phenotype after stimulation. They also exhibited dramatic morphologic differences compared with wild-type, presenting as large, ramified cells filled with vacuole-like structures. This corresponded with increased protein levels of activation markers, CD68 and beta1 integrin, in the Scna-/- cells. More importantly, Scna-/- microglia, after stimulation, secreted elevated levels of proinflammatory cytokines, TNFalpha (tumor necrosis factor alpha) and IL-6 (interleukin-6), compared with wild type. However, despite the reactive phenotype, Scna-/- cells had impaired phagocytic ability. We demonstrate for the first time that alpha-synuclein plays a critical role in modulating microglial activation state. We suggest that altered microglial alpha-synuclein expression will affect their phenotype as has already been demonstrated in neurons. This has direct ramifications for the contribution of microglia to the pathophysiology of disease, particularly in familial cases linked to altered alpha-synuclein expression.
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PMID:Alpha-synuclein expression modulates microglial activation phenotype. 1703 41


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