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)

C57Bl/10 ScSn mice infected with Toxoplasma gondii developed a meningoencephalitis, characterized by areas of tissue destruction and cellular infiltration including foci of neutrophils. Large numbers of cyst stages were found throughout the brain but were not always associated with inflammation. The use of immunocytochemistry to detect glial fibrillary acidic protein, an astrocyte specific marker, showed a widespread astrocyte activation. This was particularly prominent in areas of intense inflammation but cysts were negative for glial fibrillary acidic protein, indicating that astrocytes were not host cells for the bradyzoites. The use of the polymerase chain reaction to assist in the amplification of total brain RNA allowed the characterization of the cytokines being produced locally within the brains of infected animals. beta-actin transcripts were detected in all of the uninfected and infected mice. In only one of the seven uninfected control mice were other transcripts found. Transcripts for tumour necrosis factor-alpha, interleukin-1 alpha and beta, interleukin-6, macrophage inflammatory protein-1 and interferon-gamma as well as the CD4 marker were detected in all of the infected mice. However, transcripts for IL-2 and IL-4 were not present. Several of the cytokines present are capable of initiating meningeal inflammation and may play a role in the immunopathogenesis of toxoplasmic encephalitis.
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PMID:Detection of cytokine mRNA in the brains of mice with toxoplasmic encephalitis. 143 33

Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF), two multifunctional cytokines, recently have been identified as physiological inducers of hematopoietic cell differentiation which also induce terminal differentiation and growth arrest of the myeloblastic leukemic M1 cell line. In this work, it is shown that c-myc exhibited a unique pattern of expression upon induction of M1 terminal differentiation by LIF or IL-6, with an early transient increase followed by a decrease to control levels by 12 h and no detectable c-myc mRNA by 1 day; in contrast, c-myb expression was rapidly suppressed, with no detectable c-myb mRNA by 12 h. Vectors containing the c-myc gene under control of the beta-actin gene promoter were transfected into M1 cells to obtain M1myc cell lines which constitutively synthesized c-myc. Deregulated and continued expression of c-myc blocked terminal differentiation induced by IL-6 or LIF at an intermediate stage in the progression from immature blasts to mature macrophages, precisely at the point in time when c-myc is normally suppressed, leading to intermediate-stage myeloid cells which continued to proliferate in the absence of c-myb expression.
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PMID:Interleukin-6- and leukemia inhibitory factor-induced terminal differentiation of myeloid leukemia cells is blocked at an intermediate stage by constitutive c-myc. 190 40

During the acute phase response to bacterial endotoxin in rats, hepatic levels of cytochrome P450IIC12 [AH, reduced flavoprotein:oxygen oxidoreductase (RH hydroxylating), EC 1.14.14.1] (P450IIC12) apoenzyme and mRNA are suppressed. We set out to determine the effects of potential humoral mediators of inflammation on the expression of P450IIC12 in female rats. A single injection of 12,000 or 60,000 units of interleukin-1 alpha had no effect on total cytochrome P450 content or P450IIC12 mRNA measured 12 hr later, although P450IIC12 apoenzyme was slightly but significantly increased by the higher dose. In the second experiment, animals were given dexamethasone (100 micrograms/kg at -30 min), interleukin-1 alpha (30,000 units/kg at 0, 2, and 4 hr), or both and were sacrificed at 12 hr. Treatment with interleukin-1 alpha alone significantly suppressed total cytochrome P450, P450IIC12 apoenzyme, and P450IIC12 mRNA to 77, 53, and 65% of control levels, respectively; beta-actin mRNA was significantly increased (206% of control levels). Treatment with dexamethasone alone suppressed total cytochrome P450 and P450IIC12 mRNA (73% of controls) but did not significantly affect P450IIC12 apoenzyme measured 12.5 hr later. Again, beta-actin mRNA was increased. When both interleukin-1 alpha and dexamethasone were given, total cytochrome P450 and P450IIC12 mRNA (43% of controls) were suppressed, and beta-actin mRNA was significantly increased. In the third experiment, animals were injected at 0 and 12 hr with dexamethasone (83 micrograms/kg), interleukin-6 (33 micrograms/kg), or both. Interleukin-6 alone did not significantly affect total cytochrome P450 or P450IIC12 apoenzyme or mRNA. Dexamethasone alone suppressed P450IIC12 apoenzyme and mRNA (to 52 and 41%, respectively, of controls). Treatment with both interleukin-6 and dexamethasone significantly suppressed total cytochrome P450 and P450IIC12 apoenzyme and mRNA; suppression of P450IIC12 mRNA (to 16% of controls) was greater than with dexamethasone alone. No change in the transcription rate of CYP2C12 was observed 24 hr after initiation of treatment with dexamethasone (83 micrograms/kg at 0 and 12 hr) or 12 hr after initiation of treatment with interleukin-1 alpha (30,000 units/kg at 0, 2, and 4 hr). We conclude that, in this model, interleukin-1 alpha and glucocorticoids are important mediators of the suppression of hepatic P450IIC12 expression during inflammation. Interleukin-6 was not as potent, but it did potentiate the effects of dexamethasone. Suppression of P450IIC12 expression by dexamethasone and interleukin-1 alpha appeared to be mediated at a pretranslational level, but the possibility of a transcriptional effect needs to be further investigated.
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PMID:Regulation of cytochrome P450IIC12 expression by interleukin-1 alpha, interleukin-6, and dexamethasone. 201 47

We have previously reported that sustained tumor necrosis factor (TNF)-alpha expression is suppressed by temperatures in the febrile range in human macrophages. In this study, we examined the mechanisms of high-temperature-induced macrophage TNF suppression in the RAW 264.7 macrophage cell line. Incubating lipopolysaccharide (LPS)-stimulated RAW 264.7 cells at 40 degrees C reduced TNF secretion by 92% and peak TNF mRNA levels by 43% compared with cells incubated at 37 degrees C (P < 0.05) but did not affect levels of glyceraldehyde-3-phosphate dehydrogenase, beta-actin, or interleukin-6 mRNA. TNF mRNA half-life, measured after transcriptional arrest with actinomycin D, was reduced from 21.8 +/- 3.6 min in LPS-stimulated RAW 264.7 cells at 37 degrees C to 16.0 +/- 1.8 min at 40 degrees C (P < 0.03), but these cells at 40 degrees C did not alter transcription rate or TNF mRNA polysome association. TNF mRNA destabilization occurred at temperatures below the threshold (43 degrees C) for the generalized heat shock response in these cells. We conclude that heating macrophages to febrile-range temperatures attenuates sustained TNF expression by modulating posttranscriptional processing, including acceleration of TNF mRNA decay.
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PMID:Warming macrophages to febrile range destabilizes tumor necrosis factor-alpha mRNA without inducing heat shock. 749 2

The ability to detect feline cytokine expression would allow further characterization of the feline immune system. Bioassays are currently available for the measurement of feline IL2, IL6 and TNF alpha but not for other biologically important cytokines. To detect the expression of other cytokines, a reverse transcription-polymerase chain reaction (RT-PCR) procedure was developed. Since feline cytokine gene sequences other than TNF alpha were not available, mammalian DNA and mRNA sequences for IL2, IFN gamma, IL4, IL6, IL10, IL12 and beta-actin, obtained from the Genbank database were compared and oligonucleotide primers chosen from consensus sequences. To validate the cytokine and beta-actin primers, peripheral blood mononuclear cells from specific pathogen free (SPF) cats were cultured in the presence of Con A for various periods of time (0-72 h). RNA was collected, reverse transcribed into cDNA, and the cDNA was amplified by PCR with each set of cytokine primer pairs. RT-PCR products were hybridized with specific 32P end-labeled internal oligonucleotide probes and then analyzed with the AMBIS imaging system to determine the kinetics of cytokine mRNA production. The beta-actin signal was used to control for sample to sample variation in the quantity of mRNA and variation in the RT and PCR reactions. Peak mRNA expression for most cytokines was found to occur between 2 to 4 h of Con A stimulation. mRNA expression was correlated with cytokine bioactivity for IL2 and IL6. Peak IL2 bioactivity occurred after 8 h of Con A stimulation, 4 h after the mRNA expression had peaked. Although IL6 mRNA expression peaked between 2 and 4 h of stimulation, bioactivity was not detected until 8 h of stimulation and continued to increase over the next 24-48 h.
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PMID:A reverse transcription-polymerase chain reaction technique to detect feline cytokine genes. 760 28

In order to enhance recombinant protein productivity in animal cells, we developed the oncogene activated production (OAP) system. The OAP system is based on the premise that oncogenes are able to enhance promoter activity. To this end, we constructed reported plasmids by fusing various promoters to the human interleukin-6 (hIL-6) cDNA, and the effector plasmids by inserting individual oncogenes, for example c-myc, c-fos, v-jun, v-myb and c-Ha-ras, downstream from the human cytomegalovirus immediate early (CMV) promoter. Results of transient expression experiments with BHK-21 cells suggest that the CMV promoter is the most potent promoter examined and that the ras product is able to transactivate the beta-actin, CMV and SR alpha promoters. Recombinant BHK-21 cells producing hIL-6 under the control of the CMV promoter were contransfected with the ras oncogene and dihydrofolate reductase gene, then selected with 50 nM methotrexate to coamplify the ras oncogene. We were able to rapidly establish a stable and highly productive clone which exhibited a 35-times higher production rate as compared to the control value.
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PMID:Ras oncogene enhances the production of a recombinant protein regulated by the cytomegalovirus promoter in BHK-21 cells. 776 45

Rejection continues to be a major cause of graft loss in small intestine transplantation (SIT). We have studied, by semiquantitative reverse transcriptase PCR (rtPCR), the intragraft expression of cytokines relevant to rejection in a rat model. Heterotopic SIT grafts were performed from Lewis x Brown Norway F1 donors into Lewis recipients. The isograft control was Lewis into Lewis. Five animals in each isograft and allograft group were sacrificed on POD 3, 5, 7, 8, 9, 10, 12, and 14. mRNA was isolated from portions of the terminal ileum and rtPCR performed to amplify message for interleukin-2 (IL-2), IL-2 receptor (IL-2R), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). Semiquantitative analysis was performed using 32P radionuclide incorporation and scintillation counting. The results were expressed as percent activity compared with beta-actin. Histologic correlation with cytokine expression was made. On POD 3 after SIT there was no evidence of rejection by histology and all cytokines studied showed no difference between the isograft and the allograft. On POD 5 the first evidence of mild rejection was seen on histology and IL-6, IFN-gamma, TNF-alpha showed a significant up regulation in the allograft that persisted through POD 14. mRNA for IL-2 was not significantly upregulated until POD 7 and persisted until POD 14. IL-2R was constitutively expressed in both isograft and allograft and was not a reliable predictor of rejection. Histologic rejection was moderately severe by POD 7 and severe between POD 8 and 14 correlating with the increasing expression of IL-6, IFN-gamma, and TNF-alpha. In summary, we have shown that increasing expression of mRNA for IL-6, IFN-gamma, and TNF-alpha not only correlated with severity of rejection but that upregulation began early when histologic evidence of rejection first occurred.
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PMID:The correlation of intragraft cytokine expression with rejection in rat small intestine transplantation. 794 Jun 88

Detection of rejection after small intestine transplantation (SIT) is difficult, relying largely on histopathology. The purpose of this study was to determine if the intragraft expression of messenger RNA (mRNA) for interleukin-2 receptor (IL-2R), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF) correlated with rejection in a unidirectional, heterotopic rat SIT model. Graft samples were obtained on postoperative day (POD) 3, 5, 7, 8, 9, 10, 12, and 14. After staining, formalin-fixed samples were blindly evaluated for rejection. Reverse transcriptase polymerase chain reaction (rtPCR) using primers specific for beta-actin, IL-2R, IL-6, and TNF was performed on liquid nitrogen-frozen samples. Semiquantitation was accomplished using radionuclide incorporation and beta-scintillation counting. Intestinal histopathology in all isografts (ISO) and POD 3 allografts (ALLO) was normal. Rejection progressed in ALLO from mild on POD 5 to severe by POD 8. rtPCR analysis revealed constitutive expression of IL-2R mRNA in both ISO and ALLO. TNF and IL-6 demonstrated significant increases in mRNA expression in ALLO compared to ISO beginning on POD 5. In summary, intragraft expression of IL-2R mRNA demonstrated late up-regulation in ALLO which did not correlate with rejection. TNF and IL-6 mRNA expression predicted rat SIT rejection. rtPCR analysis of TNF and IL-6 may serve as a useful diagnostic adjunct for rat SIT rejection.
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PMID:Intragraft expression of messenger RNA for interleukin-6 and tumor necrosis factor-alpha is a predictor of rat small intestine transplant rejection. 804 Nov 28

The suppression by the synthetic glucocorticoid dexamethasone of the expression of interleukin-1 beta and interleukin-6 was examined in alveolar macrophages from cows. The expression of interleukin-1 beta mRNA was inhibited by treatment with dexamethasone for 16 hours in a dose-dependent fashion. The values of the concentration causing 50 per cent inhibition were in the range of 10(-9) to 10(-8) M. Dexamethasone similarly inhibited the expression of interleukin-6 mRNA by 50 per cent at a concentration of approximately 10(-8) M. In the concentration range from 10(-12) to 10(-4) M, dexamethasone had no effect on the expression of beta-actin. These results suggested that glucocorticoids may be involved in the regulation of the expression of interleukin-1 beta and interleukin-6 by the alveolar macrophages of cows.
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PMID:Inhibition by dexamethasone of interleukin-1 beta and interleukin-6 expression in alveolar macrophages from cows. 852 83

Lactoferrin (Lf) has been found in most biological fluids including amniotic fluid and cervical mucoids in pregnant women, and released from neutrophils in response to the inflammation. As Lf possesses antimicrobial properties, it is widely considered to be an important component of the host defence against microbial infections. It is known that premature labor is caused by amniotic infection with the increase of prostaglandin production. High concentration of the inflammatory cytokines: interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) in the amniotic fluid has been known. However, changes of Lf in amniotic fluid with infection has not been reported. In the present study, Lf concentrations in amniotic fluid were measured under the intra-uterine infections state and the biological significance of Lf was investigated. The effects of Lf on the IL-6 and IL-6mRNA production in cultured amnion cells were also investigated. The concentrations of Lf and IL-6 in amniotic fluid with CAM were 8.76 +/- 0.65 micrograms/ml and 6.92 +/- 4.88 ng/ml (n = 28) respectively and both were significantly higher (p < 0.01) than those without CAM [0.86 +/- 0.81 microgram/ml and 0.34 +/- 0.25 ng/ml (n = 31)]. Significant positive correlation (r = 0.91, p < 0.01) between Lf and IL-6 levels in amniotic fluid was found. IL-6 production induced by lipopolysaccharide (LPS) (100 ng/ml) in cultured amnion cells was significantly inhibited (p < 0.05) under the physiological concentration of Lf in amnion. Total RNA was extracted from the amniotic cells by guianizine solution. RT-PCR procedure and product analysis were performed from one microgram aliquote of total RNA. beta-actin was used as an international standard and c-DNA samples were followed by 30 cycles of PCR. RT-PCR product of IL-6 mRNA was detected by Southern hybridization. Expression of IL-6 mRNA was inhibited by the addition of Lf. From the results, the possibility that Lf might suppress amniotic IL-6 production under the condition of amniotic infection is suggested. It is also suggested that Lf might act as self defence mechanism from intra-uterine infection.
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PMID:Lactoferrin and interleukin-6 interaction in amniotic infection. 978 69


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