Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA encoding NF-IL6, an interleukin-6 (IL-6)-regulated human nuclear factor of the C/EBP family, is demonstrated to complement the transactivation function of E1A. The endogenous NF-IL6 level varies according to cell type and correlates positively with an IL-6-regulated cellular E1A-substituting activity that was described recently (J.M. Spergel and S. Chen-Kiang, Proc. Natl. Acad. Sci. USA 88:6472-6476, 1991). When expressed by transfection in cells which contain low levels of NF-IL6 and are incapable of complementing the function of E1A proteins, NF-IL6 also transactivates the E1A-responsive E2ae and E1B promoters, to the same magnitude as E1A. Activation by NF-IL6 is concentration dependent and sequence specific: mutational studies of the E2ae promoter suggest that the promoter-proximal NF-IL6 recognition site functions as a dominant negative regulatory site whereas the promoter-distal NF-IL6 recognition site is positively regulated at low NF-IL6 concentrations and negatively regulated when the NF-IL6 level is high. Consistent with these functions, NF-IL6 alone is sufficient to complement an E1A deletion mutant dl312 in viral infection, when expressed at appropriate concentrations. These results identify NF-IL6 as a sequence-specific cellular nuclear factor which regulates E1A-responsive genes in the absence of E1A.
 ...
PMID:NF-IL6, a member of the C/EBP family, regulates E1A-responsive promoters in the absence of E1A. 130 87

Interleukin-6 (IL-6) is a multifunctional cytokine which acts on a wide variety of cells, regulating immune response, acute phase reaction and hematopoiesis. In accordance with its pleiotropic functions, IL-6 is indicated to be involved in the pathogenesis of several diseases including autoimmunities, lymphoid malignancies and inflammations. An elevated level of IL-6 is demonstrated in patients with rheumatoid arthritis and cardiac myxoma, which can explain symptoms of these diseases, such as autoantibody production and increase in acute phase proteins. Therefore, inhibitors of IL-6 production or IL-6 receptor-mediated signal transduction may be used for treatment of IL-6-related diseases. The IL-6 receptor system consists of two membrane proteins, a ligand-binding chain (IL-6R) and a non-ligand-binding signal transducer, gp130, both of which belong to the cytokine receptor family. Binding of IL-6 to IL-6R triggers the association of IL-6R and gp130, and gp130 in turn transduces the signal. A nuclear factor for controlling IL-6 gene expression (NF-IL6) is also involved in the transcriptional regulation of various acute-phase protein genes. IL-6-stimulation of hepatocytes, through modification of pre-existing NF-IL6 protein, leads to binding of NF-IL6 to IL-6-responsive elements and activation of acute-phase protein genes. NF-IL6 is shown to recognize the enhancer core sequence of several viruses, suggesting a possible relationship of virus infection and IL-6 expression.
 ...
PMID:Interleukin-6 and its receptor in autoimmunity. 138 Feb 41

Interleukin-6 (IL-6) is one of the cytokines produced by human alveolar macrophages, lung parenchyma, and other cells in response to injury and infection. We hypothesized that IL-6 is released from poorly preserved lung grafts and may serve as a marker of preservation injury. Sixteen patients who received lung allografts were enrolled in this study. The average ischemic time was 284 +/- 78 minutes. Serum IL-6 level was measured before and at 4 and 24 hours after reperfusion of the grafts by an enzyme-linked immunosorbent assay. Preservation injury was assessed by (1) the need for prolonged intubation (> 7 days), (2) the arterial/alveolar oxygen tension ratio (PaO2/PAO2 ratio) at 4 hours after graft reperfusion (only in heart-lung or double lung recipients), (3) the presence of diffuse alveolar damage on first lung biopsy, and (4) the 30-day graft survival rate. IL-6 level peaked at 4 hours after reperfusion and returned to baseline at 24 hours. The patients were divided into group I (n = 6) and group II (n = 10), depending on whether the 4-hour IL-6 level was more than 1000 pg/ml or less than 500 pg/ml, respectively. Group I patients required longer intubation (p < 0.01) and had a lower PaO2/PAO2 ratio (p < 0.001), more diffuse alveolar damage (p < 0.01), and a lower graft survival rate (p < 0.01) than those of group II. No bacterial, fungal, or viral infection was found during postoperative week 1 in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interleukin-6, a marker of preservation injury in clinical lung transplantation. 145 25

Viral infection has been suggested to play a triggering role in the pancreatic beta cell destruction which occurs in insulin-dependent diabetes (IDDM). However, the underlying mechanism of this phenomenon is unknown. In this study a human insulinoma cell line has been infected with measles, mumps and rubella viruses since a temporal association is reported between the clinical onset of IDDM and diseases caused by these viruses. The infection with measles and mumps viruses induced the release of interleukin-1 (IL-1) and interleukin-6 (IL-6) by the cell line as assessed by a bioassay and up-regulated the expression of human leucocyte antigen (HLA) class I and class II antigens as evaluated by cytofluorimetric analysis. Stimulation with rubella virus induced the release of IL-6 only and had no effect on HLA antigen expression. These data show for the first time that IL-1 and IL-6 secretion by an insulinoma cell line may occur after viral infection and suggest that cytokine release and increased expression of HLA molecules by beta cells may act to induce the immune response towards beta cells in IDDM.
 ...
PMID:Viral infection induces cytokine release by beta islet cells. 159 39

It has been demonstrated that the liver loses its capacity to metabolise and eliminate drugs during viral infection or during the operation of host defence mechanisms. This loss in drug metabolism is due to the loss of the cytochrome P-450 component of the mixed function oxidase (the enzyme system primarily responsible for the oxidation of drugs, carcinogens and certain classes of endogenous substances such as steroids, fatty acids and prostaglandins). At present we have identified interferon and factors such as interleukin-1, interleukin-6 and tumour necrosis factor, released from Kupffer cells, as major mediators of the loss. The depression that occurs during viral infection is mediated via the production of interferon. This action of interferon requires the synthesis of an intermediate/s yet to be identified. The molecular mechanism for the decrease in cytochrome P-450 mediated drug metabolism during episodes of viral infections is caused by an interferon-mediated loss in mRNA and subsequent cytochrome P-450 synthesis in the liver.
 ...
PMID:Alteration of drug biotransformation by interferon and host defence mechanism. 170 43

The structures of two vaccinia virus genes (B15R and B18R) from near the right inverted terminal repeat are described. These genes encode proteins of 36.5K and 40.7K, respectively, which have an N-terminal hydrophobic sequence, possible sites for attachment of N-linked carbohydrate and a short string of hydrophobic residues near the C terminus. These properties are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons established that the two gene products are related to each other (20% identity) and to the immunoglobulin (Ig) superfamily. Intriguingly, the nearest homologues of these proteins in the SWISS-PROT (version 14) database are the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. The product of one of these genes is known to be expressed on the cell surface early during infection and immunity directed against it confer resistance to virus infection without directly neutralizing virus infectivity. We propose a novel method for virus immune evasion in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6 and prevent these cytokines reaching their natural receptors. In consequence the inflammatory response would be diminished and virus replication enhanced.
 ...
PMID:Two vaccinia virus proteins structurally related to the interleukin-1 receptor and the immunoglobulin superfamily. 182 22

The cytokine which is now called interleukin-6 (IL-6) has emerged as a major systemic alarm signal produced by essentially every injured tissue in response to almost every kind of damage. The hallmark of IL-6 gene regulation is its induction in many different tissues by inflammation-associated cytokines, bacterial products, virus infection and by activation of any of the three major signal transduction pathways (diacylglycerol, cAMP and Ca2(+)-activated). Many of these inducers act largely through a 23 base-pair "multi-response element" in the IL-6 promoter. Different tissues secrete multiple post-translationally modified forms of IL-6 (six protein species in the size range 23 to 30 kDa, and additional forms of size greater than or equal to 45 kDa). IL-6 plays a key role in activating a variety of host defence mechanisms that are aimed at limiting tissue injury. Thus, IL-6 elicits major changes in the biochemical, physiological and immunological status of the host (e.g. the "acute phase" plasma protein response). IL-6 enhances plasma protein gene expression not only in hepatocytes but also in monocytes, fibroblasts and lymphocytes. Elevated levels of IL-6 are observed in body fluids during acute and chronic infections, neoplasia and autoimmune diseases. The nature of the IL-6 receptor in hepatic and non-hepatic cells, the different signal transduction pathways involved in the regulation of particular liver genes by IL-6, the association between IL-6 levels in body fluids and clinical outcome and between IL-6 haplotypes and specific disease states remain to be explored in detail.
 ...
PMID:Interleukin-6: a regulator of plasma protein gene expression in hepatic and non-hepatic tissues. 218 60

The cytokine interleukin-6 (IL-6) has emerged as a major systemic alarm signal which appears to be produced by essentially every injured tissue. Recent evidence points to the skin, particularly the injured skin, as one of the major sites of IL-6 production. The hallmark of IL-6 gene regulation is its induction by inflammation-associated cytokines, bacterial products, virus infection, and activation of any of the three major signal transduction pathways (diacylglycerol-, cAMP-, and Ca(++)-activated). Many of these inducers act largely through a 23-bp "multiple-response element" in the IL-6 promoter. Different cell types, including keratinocytes, secrete multiple post-translationally modified forms of IL-6. This cytokine, in turn, plays a key role in activating a variety of local and systemic host defense mechanisms that are aimed at limiting tissue injury. Thus, IL-6 elicits major changes in the biochemical, physiologic, and immunologic status of the host (e.g., the "acute phase" plasma protein response; activation of B, T, and NK-cell function). IL-6 enhances the proliferation of human keratinocytes and of many B-cell lines but inhibits that of certain carcinoma cell lines; nevertheless, IL-6 can enhance the motility of these carcinoma cells. Elevated levels of IL-6 are observed in human body fluids during acute and chronic infections, neoplasia, autoimmune diseases, and psoriasis and following third-degree burns. It is likely that IL-6 produced by cellular elements in the skin represents an important means of communication between the external environment and the millieu interieur.
 ...
PMID:Interleukin-6: molecular pathophysiology. 219 Oct 52

Interleukin-6 (IL-6) activity was measured in the cerebrospinal fluid (CSF) of patients at different stages of human immunodeficiency (HIV) virus infection and of patients with multiple sclerosis (MS) or other inflammatory (OID) and noninflammatory neurological diseases (OND). In the advanced stages of HIV infection and in OID, IL-6 was detected more frequently (80 and 75% of the cases) and at higher concentrations than in the early stages of HIV infection. MS and OND (44, 48, and 44% of cases). Analysis of CSF and paired sera indicated that IL-6 production can be compartmentalized to either of the fluids. Evidence that altered blood-brain barrier functions can, at least in part, influence the CSF IL-6 levels was found in OID patients. No association was evident between intrathecal immunoglobulin synthesis and CSF IL-6 levels. Interleukin-1 (IL-1) levels were detectable in a minority of the samples from neurological patients; one OID patient had high levels of both CSF IL-1 and IL-6.
 ...
PMID:Cerebrospinal fluid interleukin-6 activity in HIV infection and inflammatory and noninflammatory diseases of the nervous system. 220 5

Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded polyribonucleotide that elicits immune responses analogous to those observed during viral infection. It is also known to modulate the expression of certain autoimmune disorders including diabetes mellitus in the BB rat and NOD mouse. The mechanism underlying these immunomodulatory effects is not known, but it could involve activation of vascular endothelium. We now report that parenteral poly I:C induces rat pancreatic endothelium to hyperexpress intercellular adhesion molecule 1 (CD54). This is accompanied by a perivascular recruitment of mononuclear cells to the exocrine pancreas. Corollary in vitro studies demonstrated that poly I:C is a potent activator of both rat and human endothelial cells in culture. It upregulates endothelial expression of several leukocyte adhesion molecules, stimulates the release of interleukin-6 and interleukin-8, and antagonizes interferon-gamma induction of major histocompatibility complex class II expression. We conclude that poly I:C activates endothelial cells to express surface molecules and cytokines in a pattern classically associated with leukocyte recruitment. These effects may in part contribute to the immunomodulatory effects of poly I:C in animal models of autoimmunity.
 ...
PMID:Polyinosinic:polycytidylic acid is a potent activator of endothelial cells. 751 92


1 2 3 4 5 6 7 8 9 10 Next >>