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)

Interleukin-6 (IL-6) has various biological activities including growth stimulation and maturation of B cells into antibody-producing cells, growth stimulation of murine hybridoma and plasmacytoma cells, induction of acute phase proteins, activation of T cell functions, triggering differentiation of various hematopoietic cells, and inhibition of growth of the human ductal breast carcinoma cell line T-47. Recently it was found that IL-6 also has the ability to enhance natural killer (NK) cell activity. In the present study the possible role of IL-6 as a regulator of NK cell-mediated cytotoxicity (NK-CMC) was evaluated. It was found that IL-6 reduced the sensitivity of T-47 cells (a ductal breast carcinoma cell line) to NK-CMC. The mechanism of IL-6-induced protection was studied. IL-6 had no effect on the level of conjugate formation between T-47 cells and NK cells. However, IL-6 reduced the number of dead conjugated T-47 cells. IL-6-treated T-47 cells were also found to be as sensitive as the nontreated cells to the lytic effect of NK cytotoxic factor (NKCF). However, IL-6 appeared to reduce the ability of T-47 cells to induce release of NKCF from NK cells following conjugate formation. Therefore, it is suggested that IL-6 protects T-47 cells from natural killing by the same mechanism as interferon.
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PMID:Interleukin-6 protects ductal breast carcinoma cells from MHC-unrestricted cell-mediated cytotoxicity. 132 93

Monocytes potentially express two mRNA species by alternative splicing of exons at the 5' end of the gene. During inflammation the plasma concentration of AAT can increase about three-fold. In a myelomonocytic cell line (U937), under basal conditions, two AAT mRNA species are produced. After stimulation by interleukin-6 (IL-6) one mRNA species is produced resulting from the exclusion of the second monocyte exon. These findings demonstrate a novel way in which the expression of mRNA can be modified in a single cell type.
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PMID:Exclusion of an exon in monocyte alpha-1-antitrypsin mRNA after stimulation of U937 cells by interleukin-6. 224 95

We analyzed serum levels of interleukin-6 (IL-6) and seven acute phase proteins in CRP positive samples and in patients with open heart surgery. The concentrations of serum IL-6 were not correlated with other acute phase proteins in CRP positive samples. However, IL-6 were in inverse correlation with CRP, AAG, AAT and CER in patients with open heart surgery. These discrepancies were due to the differences in response time of each acute phase protein after the start of inflammation. Responses of acute phase proteins after open heart surgery were investigated from hour to hour. IL-6 increased rather rapidly than other acute phase proteins, and increases of CRP, TRF, AAT, AAG, CER, HAP and AMG followed. The time reached the peak were IL-6, CRP, TRF, AAT, AMG, AAG, HAP reached the peak in that order. IL-6 constantly increased seven hours earlier, and reached at maximum values forty three hours earlier than CRP in each case. The measurement of serum concentration of IL-6 may be useful for early detection of acute inflammation.
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PMID:[The clinical significance of interleukin-6 as an inflammatory marker (the studies in patients with open heart surgery)]. 753 Dec 52

The acute-phase response is the answer of the organism to a disturbance of its homeostasis and is characterized by dramatic changes in the concentration of some plasma proteins defined as acute-phase proteins. In recent years several data have shown that interleukin-6 (IL-6) is the major inducer of acute-phase protein synthesis in human hepatocytes. Recently, we demonstrated higher IL-6 serum levels in head and neck cancer (HNC) patients than in healthy subjects. In the present study we examined the relationship between levels of IL-6 and of several acute-phase proteins, including C-reactive protein (CRP), alpha 1-antitrypsin (ATT), alpha 1-acid glycoprotein (AAG), haptoglobin (HPT) and fibrinogen. Eighteen patients were studied and had squamous cell carcinoma of the larynx (n = 9), oral cavity (n = 4), oropharynx (n = 3) and hypopharynx (n = 2). Proteins were measured at three time points before and three time points after surgery. Significant (P < 0.0001) relationships were found between IL-6 and CRP (r = 0.69), and fibrinogen (r = 0.51), whereas no correlation was found with AAT (r = 0.13, P = 0.56), AAG (r = 0.38; P = 0.07) and HPT (r = 0.16; P = 0.46). These data strongly suggest that IL-6 may play a key role in acute-phase protein synthesis in HNC and in regulation of the complex host response to malignancies.
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PMID:Interleukin-6 and acute-phase proteins in head and neck cancer. 754 87

Interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are the main proinflammatory cytokines responsible for the inflammatory process and cartilage destruction of inflammatory arthropathies. The present study sequentially measured the concentrations of these cytokines and their proportions of detectable levels in the synovial fluid (SF) of 23 patients with non-gonococcal (GC) septic arthritis before and after treatment. Persistently high concentrations and proportions of IL-6 and TNF-alpha were found up to day 7 of treatment, while SF IL-1beta concentration declined significantly after day 7 (p = 0.036). SF IL-1beta and TNF-alpha correlated with each other significantly and with SF WBC counts (p < 0.01). Positive correlations between SF IL-1beta concentration and joint effusion (p < 0.01) and between SF TNF-alpha concentration and joint tenderness (p < 0.001) were observed. SF IL-1beta and TNF-alpha were significantly higher in patients with local complications of septic arthritis. In conclusion, high levels of IL-1beta, IL-6 and TNF-alpha were detected in SF of patients with non-GC septic arthritis. Only IL-1beta decreased significantly after day 7 of treatment, but IL-6 and TNF-alpha concentrations were persistently high. SF IL-1beta and TNF-alpha may be useful in predicting the outcome and complications of patients with this disease.
Asian Pac J Allergy Immunol 1998 Dec
PMID:IL-1beta, IL-6 and TNF-alpha in synovial fluid of patients with non-gonococcal septic arthritis. 1021 96

alpha(1)-Antitrypsin (AAT) is the major serine proteinase inhibitor (SERPIN A1) in human plasma. Its target proteinase is neutrophil elastase and its main physiological function is protection of the lower respiratory tract from the destructive effects of neutrophil elastase during an inflammatory response. Circulating levels of AAT rise 2-3-fold during inflammation and the liver produces most of this increase. The cytokines oncostatin M (OSM) and interleukin-6 have been shown to be mainly responsible for this effect, which is mediated via the interaction of cytokine-inducible transcription factors with regulatory elements within the gene. In the present study, we report for the first time that OSM stimulation of hepatocyte AAT occurs via an interaction between the hepatocyte promoter and an OSM-responsive element at the 3'-end of the AAT gene. This effect is mediated by the transcription factor signal transducer and activator of transcription 3 ('STAT 3') binding to an OSM-responsive element (sequence TTCTCTTAA), and this site is distinct from, but close to, a previously reported interleukin-6-responsive element.
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PMID:Oncostatin M induced alpha1-antitrypsin (AAT) gene expression in Hep G2 cells is mediated by a 3' enhancer. 1193 50

The serine proteinase inhibitors (serpins) are a superfamily of proteins with a diverse set of functions, including the control of blood coagulation, complement activation, programmed cell death and development. The most abundant serpins in human plasma are alpha(1)-antitrypsin (AAT) and alpha(1)-antichymotrypsin (ACT). During inflammation, circulating levels can increase by up to 3-fold for the former and by 4-5-fold for the latter. The major site for increased synthesis is the liver. Other tissues, such as the lung, are also capable of synthesizing AAT and ACT, and expression can be increased by up to 100-fold by cytokines. There is a tissue-specific promoter for the liver, and alternative promoters for other tissues that express AAT. Basal AAT expression is regulated by the synergistic action of the tissue-specific transcription factors hepatocyte nuclear factors 1alpha and 4. An enhancer positioned approx. 1.2 kb from the end of the last exon in the 3' flanking sequence modulates cytokine-induced expression by interleukin-6 and oncostatin M. Microcell hybrid transfection studies have shown that a sequence containing 15 kb of 5' flanking sequence is sufficient to allow stable expression of AAT in a position-independent manner. There is probably a single promoter for ACT. Oncostatin M-inducible elements have been identified in the 5' flanking sequence approx. 100 bp upstream from the transcription initiation site, and a further interleukin-1-responsive enhancer has been identified approx. 13 kb upstream. The pathways for a humoral response are being mapped at high resolution.
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PMID:Gene regulation of the serine proteinase inhibitors alpha1-antitrypsin and alpha1-antichymotrypsin. 1202 32

In hematopoiesis, cytokine levels modulate blood cell replacement, self-renewal of stem cells, and responses to disease. Feedback pathways regulating cytokine levels and targets for therapeutic intervention remain to be determined. Amino boronic dipeptides are orally bioavailable inhibitors of dipeptidyl peptidases. Here we show that the high-affinity inhibitor Val-boro-Pro (PT-100) can stimulate the growth of hematopoietic progenitor cells in vivo and can accelerate neutrophil and erythrocyte regeneration in mouse models of neutropenia and acute anemia. Hematopoietic stimulation by PT-100 correlated with increased cytokine levels in vivo. In vitro, PT-100 promoted the growth of primitive hematopoietic progenitor cells by increasing granulocyte-colony-stimulating factor (G-CSF), interleukin-6 (IL-6), and IL-11 production by bone marrow stromal cells. Two molecular targets of PT-100 are expressed by stromal cells- CD26/DPP-IV and the closely related fibroblast activation protein (FAP). Because PT-100 was active in the absence of CD26, FAP appears to be the hematopoietic target for PT-100. Interaction of PT-100 with the catalytic site seems to be required because amino-terminal acetylation of PT-100 abrogated enzyme inhibition and hematopoietic stimulation. PT-100 is a therapeutic candidate for the treatment of neutropenia and anemia. The data support increasing evidence that dipeptidyl peptidases can regulate complex biologic systems by the proteolysis of signaling peptides.
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PMID:Hematopoietic stimulation by a dipeptidyl peptidase inhibitor reveals a novel regulatory mechanism and therapeutic treatment for blood cell deficiencies. 1273 65

It has been suggested that a number of molecules associated with inflammation are involved in the pathogenesis of Alzheimer's disease (AD). We measured the levels of alpha(1)-antichymotrypsin (ACT), alpha(1)-antitrypsin (AAT), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and oxidised low-density lipoprotein (oxLDL) in matched cerebrospinal fluid (CSF) and plasma of 141 patients with probable AD. We found a significant relationship between CSF and plasma levels of ACT (r = 0.4, p < 0.001), IL-6 (r = 0.74, p < 0.001), MCP-1 (r = 0.71, p < 0.001), and a borderline relationship between CSF and plasma oxLDL (r = 0.22, p < 0.05). In addition, linear regression analysis revealed a positive correlation between levels of CSF-ACT and oxLDL (p < 0.001), but an inverse relation between levels of CSF ACT, CSF AAT and MCP-1 (p < 0.001). A significant correlation was also found between levels of CSF ACT, oxLDL and the ratio of CSF to serum albumin, which is used as a measure of the blood-brain barrier function. Our data extend previous reports regarding the inflammatory markers in the plasma and CSF of patients with AD and provide good evidence that levels of ACT, IL-6, MCP-1 and oxLDL in plasma and CSF might be candidates as biomarkers for monitoring the inflammatory process in AD.
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PMID:Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer's disease. 1282 39

The regulation of human haematopoiesis is a complex biological system with numerous interdependent processes. In vivo Haematopoietic Stem Cells (HSCs) self-renew so as to maintain a constant pool of these cells. It would be very interesting to maintain these cells in vitro, in view of their therapeutical importance. Unfortunately, there is currently no known process to activate HSCs self-renewal in vitro. Since the difficulties related to in vitro experiments, modeling and simulating this process is indispensable. Moreover, the complexity of haematopoiesis makes it necessary to integrate various functionalities: both discrete and continuous models as well as consumption and production of resources. We thus focus on the use of Hybrid Functional Petri Nets, which offer a number of features and flexibility. We begin by modeling and simulating the role of a specific cytokine, interleukin-6, in the regulation of early haematopoiesis. Results obtained in silico lead to the disappearence of HSCs, which is in agreement with in vitro results.
Pac Symp Biocomput 2006
PMID:Modeling and simulation with Hybrid Functional Petri Nets of the role of interleukin-6 in human early haematopoiesis. 1709 58


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