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)

The replication genes (rep) of the virulence plasmid pYVe439-80 of Yersinia enterocolitica were localized and characterized by restriction endonuclease analysis. Comparison with pIB1, a virulence plasmid of Y. pseudotuberculosis, indicates that while the plasmids carry homologous rep genes their location with respect to the highly conserved 'calcium region' is different. This replication function is thermosensitive. Mini-derivatives of pYVe439-80 appear to be rather unstable. The region of pYVe439-80 containing homology to the incD determinant of F was shown to contain a plasmid-stabilization system (par). The region encoding par was characterized by restriction endonuclease analysis. pIB1 contained an homologous par region but located differently. The pYV plasmids thus underwent rearrangements during their divergent evolution. While the positions of rep and par in the two plasmids are inverted with respect to the surrounding loci, our determination of the orientation of each locus rules out the hypothesis of a simple inversion of a quadrant of pYV. The gene encoding YOP5, a 26 kDa protein encoded by pIB1, was cloned on a mobilizable vector and introduced in Y. enterocolitica W22708 containing pYVe227 (indistinguishable from pYVe439-80), mutated in the homologous gene. The recombinant Y. enterocolitica secreted YOP5. Hence, the transcriptional activation and secretion systems of pYVe227 act on a yop gene from pIB1 and on its product, indicating that these systems are interchangeable.
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PMID:The replication, partition and yop regulation of the pYV plasmids are highly conserved in Yersinia enterocolitica and Y. pseudotuberculosis. 322 Nov 96

Increasing evidence supports a role for cytokines as chemical signals in the CNS, either under normal conditions or in the pathologic state. CNS levels of the cytokine interleukin-6 (IL-6) are known to be elevated in several diseases associated with developmental disorders and may contribute to the pathological state. To investigate the potential role of IL-6 in such disorders, neuronal effects of IL-6 were examined during development using an in vitro model system, cultured rat cerebellar granule neurons. The cultures were prepared from 8 d postnatal rat pups and exposed chronically to IL-6 (5 ng/ml) by addition to the culture medium. Neuronal effects of IL-6 were assessed by a comparison of calcium signals produced in control and IL-6 treated neurons by the glutamate receptor agonists NMDA and domoate and by K+ depolarization. IL-6 treatment significantly enhanced the response to NMDA and altered the developmental pattern of NMDA sensitivity, whereas only minor changes were observed for the response to domoate and K+. Reducing extracellular calcium and depleting intracellular stores significantly decreased the amplitude of the response to NMDA in control and IL-6 treated neurons. However, the IL-6 treated neurons were significantly more sensitive to these treatments than control neurons. These results suggest that elevated levels of IL-6 can significantly alter CNS neuron development and response to excitatory transmitters, and that IL-6 pretreatment selectively enhances the intracellular calcium responses to NMDA by altering the relative contribution of extracellular calcium influx and release of calcium from stores to the calcium signal.
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PMID:Interleukin-6 selectively enhances the intracellular calcium response to NMDA in developing CNS neurons. 747 29

In a group of 111 patients with multiple myeloma (MM) comprising a group of 34 patients examined when the diagnosis was established and a group of 77 patients evaluated in different stages of the disease, the author examined the relationship between the interleukin-6 serum level (IL-6), assessed by the method of enzyme immunoanalysis and selected laboratory indicators of the disease. Elevated IL-6 values were recorded in 38% of the patients. In neither of the groups significant relations were found between IL-6 and calcium, urea, creatinine levels, the amount and type of monoclonal immunoglobulin, lacticode dehydrogenase, beta 2-microglobulin, ferritin, IL-2 and its soluble receptor in serum and the incidence of myeloma plasmocytes in bone marrow. In the second (but not in the first) group a significant relationship was recorded between IL-6 levels and the red cell sedimentation rate, the Hb value, the CRP level and serum albumin and the value of thymidinekinase in serum of patients with a value beyond the normal range. From the investigation ensues that examination of IL-6 serum levels in MM contributes so far mainly to improvement of the diagnosis and expedient classification of this disease in clinical practice.
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PMID:[Serum interleukin-6 in multiple myeloma: I. Relation to selected laboratory indicators of disease]. 748 49

Interleukin-11 (IL-11) is a pleiotropic cytokine with important effects on hematopoietic and other cells. IL-11 was originally described as a product of stromal cell lines and fibroblasts. Using RT-PCR, Northern blotting, and ELISA we demonstrated that the human U373 and U87 glioblastoma cell lines expressed IL-11 and its encoding mRNA when stimulated with IL-1 beta, phorbol ester, and calcium ionophore. The neuroblastoma cell line SH-SY5Y did not express IL-11 mRNA in response to these agents. Cerebral expression of IL-11 by glial cells is important because IL-11 has been shown to have effects on neuronal electrophysiology, has overlapping functions with the neuroactive cytokine interleukin-6, and is part of the gp130-associated neuropoietic family of cytokines.
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PMID:Expression of interleukin-11 and its encoding mRNA by glioblastoma cells. 750 Dec 71

It has been demonstrated that thyroid hormones stimulate osteoclasts indirectly and that this effect is mediated by products of other cell types present in bone. To determine if interleukin-6 (IL-6) could be a mediator of thyroid hormone action, we investigated the effect of 3,5,3'-triiodothyronine (T3) on bone resorption (45Ca release) and on the IL-6 concentration in medium from cultured 19-day-old fetal rat limb bones. T3 alone increased 45Ca release significantly only at a fairly high concentration (10(-6)M) under the conditions used. T3 alone, over a 10(-11)-10(-6) M concentration range, failed to elicit a detectable effect on the medium IL-6 content. However, T3 potentiated the stimulatory effect of interleukin-1 beta (IL-1 beta) on IL-6 production in a dose-dependent manner. T3, 10(-8) M, also significantly increased IL-1 beta-stimulated calcium release. Inhibition of IL-1 beta with 1 muM interleukin-1 receptor antagonist (IL-1ra) abrogated the potentiating effects of T3 on IL-1 beta-stimulated IL-6 production and blocked the combined effect of T3 and IL-1 beta on 45Ca release. One micromolar indomethacin significantly, but not completely, inhibited the effect of IL-1 beta, as well as the combined effect of IL-1 beta and T3 on resorption and IL-6 production, indicating the involvement of prostaglandins in these actions. Consistent with this, 1 microM prostaglandin E1 (PGE1) significantly increased both the IL-6 production and the calcium release. By potentiating the effect of IL-1 beta, T3 increased bone resorption at much lower concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Triiodothyronine potentiates the stimulatory effects of interleukin-1 beta on bone resorption and medium interleukin-6 content in fetal rat limb bone cultures. 750 3

Mast cells produce a number of cytokines including IL-6. In view of the large amounts of de novo synthesis induced by the activation of rat peritoneal mast cells and previous observations of expression of this cytokine by human lung mast cells, we have studied the regulation of IL-6 production. We examined the hypothesis that mast cell IL-6 production is not related to previous histamine release. Highly purified rat peritoneal mast cells were activated with anti-IgE, calcium ionophore A23187, or LPS. Histamine was used as a marker of preformed mediator release and IL-6 production was assessed by using the B9 hybridoma growth factor bioassay. Anti-IgE activation of rat peritoneal mast cells induced IL-6 production and histamine release. In contrast, LPS activation induced substantial, serum-dependent, IL-6 production without a significant level of histamine release. No preformed IL-6 was detected in the cells. Calcium ionophore induced histamine release from mast cells to a greater extent than did anti-IgE, but no A23187-induced IL-6 production was observed. A23187-treated cells retained high viability and produced a significant amount of TNF-alpha. To further examine the concordance of IL-6 production and histamine release we used mast cell stabilizing drugs. Dexamethasone and nedocromil significantly inhibited IL-6 production in response to anti-IgE. Our results demonstrate that there is not a direct relationship between mast cell degranulation and IL-6 production. Our observations are important for understanding the role of mast cells in inflammation and for developing strategies to modulate mast cell function in disease.
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PMID:IL-6 production by rat peritoneal mast cells is not necessarily preceded by histamine release and can be induced by bacterial lipopolysaccharide. 751 39

Cytokines have significant roles in some cardiovascular disorders, but direct myocardial effects of cytokines remain to be elucidated. In the present study, we examined both the early and delayed effects of interleukin-6 (IL-6) on cultured chick embryo ventricular myocytes. Exposure of these cells to human recombinant IL-6 significantly decreased peak systolic [Ca2+]i (71.0 +/- 0.6% of the control value) and the amplitude of cell contraction (66.0 +/- 7.4% of the control value) within a few minutes. Pretreatment with NG-monomethyl-L-arginine (L-NMMA) or methylene blue completely inhibited the IL-6-induced early changes. Subsequent addition of L-arginine reversed the effects of L-NMMA. The levels of cGMP were significantly increased after 30 minutes of exposure to IL-6 (134.4 +/- 9.1% of the control value). Pretreatment with L-NMMA or EGTA significantly inhibited the IL-6-induced early elevation of cGMP. These results suggest that IL-6 acutely decreases intracellular Ca2+ transients and depresses cell contraction by nitric oxide (NO)-cGMP-mediated pathway. Therefore, IL-6 may enhance the Ca(2+)-dependent constitutive NO synthase activity in cardiac myocytes. On the other hand, 24-hour exposure to IL-6 also increased the levels of cGMP (159.0 +/- 22.8% of the control value) regardless of pretreatment with EGTA. These delayed increases in cGMP were also shown to be coupled with decreases in intracellular Ca2+ transients and the amplitude of cell contraction. Thus, IL-6 may induce Ca(2+)-independent NO synthase in cardiac myocytes. Together with the previous reports that have suggested the possible roles of IL-6 in myocardial stunning or endotoxic shock, this negative inotropic effect of IL-6 may contribute to these clinical settings.
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PMID:Nitric oxide-mediated effects of interleukin-6 on [Ca2+]i and cell contraction in cultured chick ventricular myocytes. 751 62

Recent evidence suggests that the level of interleukin-6 (IL-6) is elevated in Alzheimer's disease (AD) brains. IL-6 is produced by reactive glial cells and could potentially affect neuronal survival. Understanding the biochemical mechanism that regulates the production and release of IL-6 by astrocytic cells may help to identify potential targets for therapeutic intervention in AD. In the present study, glial fibrillary acidic protein-positive human U373MG astrocytoma cells were used as a model of reactive astrocytes. Production of IL-6 in response to drug treatment was monitored with an ELISA assay. Histamine (1-100 microM), substance P (SP; 1-100 nM), and human interleukin-1 beta (IL-1 beta; 1-30 pM) stimulated the release of IL-6 in a time- and concentration-dependent manner, with EC50 values of 4.5 microM, 8 nM, and 4.5 pM, respectively. The respective effects of histamine, SP, and IL-1 beta were effectively blocked by the histamine H1, SP, and IL-1 receptor antagonists, supporting a receptor-mediated event for these agents. Both histamine and SP enhanced the formation of inositol phosphates and increase intracellular calcium levels, suggesting that the phosphatidylinositol bisphosphate/protein kinase C pathway may be involved in the IL-6 release process. Indeed, phorbol 12-myristate 13-acetate, a protein kinase C activator, also evoked IL-6 release from the U373MG cells. On the other hand, IL-1 beta, which produces a much more robust release of IL-6 than histamine or SP, has no effect on inositol phosphate formation or intracellular calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of the release of interleukin-6 from human astrocytoma cells. 751 68

In necrotizing pancreatitis a high interleukin-6 (IL-6) serum level has been proposed as a prognostic criterium. However, literature does not report any information about the role of IL-6 in the function of pancreatic acinar cells. Cholecystokinin, gastrin binding, amylase release and intracellular calcium measurement were performed on a rat pancreatoma cell line, AR4-2J, which has been recognized as a useful tool for studies on the long-term regulation of pancreatic acinar cells. The addition of IL-6 (400 pM) for 48hrs to the AR4-2J cells induced no change in the binding affinities but there was a 2 fold increase in the binding capacity of cholecytokinin (CCKA R) and gastrin (CCKB R) receptors. Although IL-6 treatment did not change directly the secretory capacity and did not activate the intracellular calcium mobilization of AR4-2J, it indirectly increased the sensitivity of the cells to the stimulation of amylase release and the intracellular calcium mobilization by cholecystokinin and gastrin. It is most likely this effect was due to the IL-6-induced increase in the numbers of CCKA R and CCKB R. Therefore this report suggests that the cytokine IL-6 acts on the CCK regulation of pancreatic enzyme secretion.
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PMID:Interleukin-6 regulation of CCK/gastrin receptors and amylase secretion in a rat pancreatic acinar cell line (AR4-2J). 753 49

Nitric oxide synthases (NOS) are enzymes that produce nitric oxide (NO) from L-arginine in a reaction yielding citrulline as a coproduct. Nitric oxide modulates the activity of a wide variety of cells, but little is known about its effects on bone cells. In the present study we report that the NOS inhibitor NG-monomethyl-L-arginine (NMMA) induced a dose-dependent inhibitory effect on the proliferation of the osteoblast-like cell lines MG63 and ROS 17/2.8. The inhibitory effect was prevented by increasing L-arginine concentrations in the medium and by the NO donor sodium nitroprusside. Likewise, NMMA inhibited interleukin-6 secretion, independently of its effect on cell number. NOS expression by MG63 cells was confirmed by measuring their ability to metabolize radiolabeled L-arginine to citrulline. NOS bioactivity was detected in unstimulated cells, but was markedly increased by stimulating the cells with cytokines, lipopolysaccharide, or 1,25-dihydroxyvitamin D3. NOS activity was partially dependent upon the presence of calcium in the medium. Furthermore, constitutive-type NOS (c-NOS) and inducible-type NOS (i-NOS) mRNA expression was detected in ROS 17/2.8 cells after reverse transcription and polymerase chain reaction amplification. In conclusion, osteoblast-like cells express c-NOS and i-NOS, and NOS activity seems to play an important role in the regulation of cell proliferation and function.
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PMID:Expression and functional role of nitric oxide synthase in osteoblast-like cells. 754 Mar 49


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