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)

Haemopoiesis is often depressed in patients suffering from acquired immune deficiency syndrome (AIDS). Although several mechanisms have been postulated to be responsible for depressed haemopoiesis in AIDS patients, the aetiology of this disorder is still unknown. We hypothesized that failure of the stromal microenvironment may account for part of the haemopoietic defect observed in patients with AIDS. We therefore studied a murine model of AIDS (MAIDS) caused by infection with LP-BM5 virus to determine the ability of bone marrow cells from immunodeficient mice to establish long-term stromal cultures. In addition, normal and MAIDS mice received AZT (2 mg/ml) in their drinking water for up to 1 month to determine the effects of AZT treatment in vivo on the ability of bone marrow cells to support haemopoiesis in long-term cultures. Decreased numbers of non-adherent cells were observed in long-term bone marrow cultures (LTBMC) of MAIDS mice when compared to cultures derived from normal mice. Decreased numbers of non-adherent cells were observed in cultures of bone marrow cells from AZT-treated normal mice, when compared to untreated normal controls. Cells from AZT-treated MAIDS mice produced the smallest number of non-adherent cells. BFU-E and CFU-G/M were decreased in cultures of MAIDS mice when compared to those of normal mice. AZT-treatment further decreased the number of colony-forming cells in both MAIDS mice and normal cultures. Stromal cell function of MAIDS mice was also assessed by inoculating non-adherent cells from normal mice onto confluent irradiated MAIDS LTBMC. Stroma from MAIDS mice was unable to support haemopoietic function of normal bone marrow cells. Polymerase chain reaction (PCR) analysis of steady state levels of cytokine mRNAs of cells from confluent cultures revealed that levels of interleukin-6 mRNA were unchanged in MAIDS mice, as compared to normal controls, but the levels of GM-CSF were decreased in MAIDS mice. These data suggest that LP-BM5 MuLV infection alters the functioning of the haemopoietic stroma and that one mechanism of this depression in haemopoiesis may be via alterations of cytokine production.
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PMID:Impaired ability of bone marrow cells from immunodeficient mice to establish long-term cultures. 791 27

Cadmium is a known immunotoxic agent in animal studies. Cells of the mononuclear phagocytic system are strategically located at portals of entry in humans and therefore may be particularly at risk for cadmium exposure through contaminated air, food, and drinking water. The purpose of this study was to determine whether there were changes in interleukin-6 (IL-6) production, a pleiotropic cytokine, when an activated human monocytic cell line was exposed to cadmium. Results suggest that there were statistically significant lower levels of IL-6 at 0.06 mM cadmium (P < 0.05), and 0.8 and 0.1 mM cadmium (P < 0.01), determined via the ELISA method. IL-6 messenger RNA (mRNA) levels were also decreased at these cadmium concentrations. The addition of a chelating agent, EDTA, to the cultures prevented the suppression of IL-6 secretion.
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PMID:Cadmium inhibits IL-6 production and IL-6 mRNA expression in a human monocytic cell line, THP-1. 801 39

Mycoplasmal products may exert a number of diverse in vitro effects on cells of the immune system. A macrophage-activating substance from Mycoplasma fermentans was described in this laboratory and named mycoplasma-derived high-molecular-weight material (MDHM). Using synthesis of nitric oxide by peritoneal cells from endotoxin low-responder mice as an assay system, MDHM was purified as follows. After freeze-thawing of M. fermentans, MDHM activity was sedimented with the membrane fraction. Membranes were delipidated with chloroform-methanol, and MDHM activity was extracted with octyl glucoside. Coextracted proteins were degraded by proteinase K. MDHM was further purified by reversed-phase high-pressure liquid chromatography and eluted in one major and one minor peak of activity. Neither carbohydrates nor amino acids were found as constituents. MDHM had the following properties: it partitioned into the phenol phase upon phenol-water extraction and into the Triton phase after extraction with Triton X-114. MDHM was not inactivated by either phospholipase A2 or triglyceride lipases. However, mild periodate treatment led to a > 95% loss of activity. Also, alkaline hydrolysis at 25 degrees C completely abolished MDHM activity with a half-life of 2 min. MDHM activity was spread out over a wide molecular weight range upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membranes, whereas after proteinase treatment MDHM activity migrated close to the front. These features of MDHM, taken together, speak in favor of an amphiphilic molecule with a lipid moiety carrying fatty acids in ester linkage and a polyol moiety of unknown character. MDHM was active in the nanogram-per-milliliter range, activating macrophages to release nitric oxide, interleukin-6, and tumor necrosis factor.
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PMID:Purification and partial biochemical characterization of a Mycoplasma fermentans-derived substance that activates macrophages to release nitric oxide, tumor necrosis factor, and interleukin-6. 806 96

Modification of recombinant murine interleukin-6 (mIL-6) with the tryptophan-specific reagent 2-nitrophenylsulfenyl chloride under mild acidic conditions, 0.1 M sodium acetate, pH 3.5, yielded a derivative containing 2.02 mol 2-nitrophenylsulfenyl tryptophan/mol protein. The sites of modification were identified as Trp36 and Trp160. No detectable side reactions occurred on other amino acids in the molecule, as indicated by the combination of endoproteinase Asp-N peptide mapping, Edman degradation and electrospray mass spectrometry. Sulfenylation of the two tryptophan residues in mIL-6 caused a 50% reduction in both the biological activity in the murine-hybridoma-growth-factor assay using 7TD1 cells and receptor-binding affinity to mIL-6 receptors. Sulfenylation of mIL-6 did not significantly affect the overall conformation of the protein as measured by farultraviolet circular dichroism and binding to the neutralizing anti-mIL-6 mAb 6B4. The sulfenylated protein was, however, significantly less stable [delta delta G(H2O) = 3.98 kJ/mol] than unmodified mIL-6 as measured by urea-gradient gel electrophoresis.
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PMID:Specific covalent modification of the tryptophan residues in murine interleukin-6. Effect on biological activity and conformational stability. 822 86

Temporal patterns of the cachectic effects of tumor growth and their relation to systemic levels of tumor necrosis factor (TNF) and IL-6 (interleukin-6) were examined in a rat model of experimental cancer cachexia employing the methylcholanthrene (MCA) sarcoma. Fischer 344 rats, implanted with biotelemeters for measuring temperature and activity, were implanted subdermally with tumor tissue fragments. Ad libitum-fed and pair-fed controls were sham incised. Bioassays for TNF and IL-6 were performed on serial plasma samples, obtained via jugular vein at 3- to 6-day intervals throughout the experimental period. Tumor growth induced significant anorexia, weight loss, and a decline in motor activity corresponding to an increase in mean plasma IL-6 levels, independent of reduced food intake or weight loss alone as shown in pair-fed controls. A significant lowering of body temperature then developed, followed by a two- to threefold increase in water consumption. The patterns of weight loss and temperature reduction differed in rate and degree from those seen with pair feeding.
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PMID:Experimental cachexia: effects of MCA sarcoma in the Fischer rat. 836 92

The coupling of isoelectric focusing on immobilized pH gradients (IPG) with electrospray-mass spectrometry (ES-MS) was applied to the characterization of proteins according to two different and important properties, such as net surface charge and molecular mass. From a technical point of view, these methods are complementary, since ES-MS requires ion-free samples as usually supplied by isoelectric focusing on IPGs. This report describes the experiments carried out on model proteins to demonstrate the feasibility of the sequential application of these two techniques for the characterization of proteins. A minimum of 5 micrograms protein was needed for good signal by mass spectrometry. The following proteins were studied: myoglobin, truncated interleukin-6-mutein, recombinant cytochrome c551 and insulin-like growth factor I. Extraction from the IPG matrix was carried out in 70% acetonitrile/30% water/0.05% trifluoroacetic acid either by passive diffusion or by centrifugation through a 0.22 micron Amicon membrane, with protein recoveries of 80-85%.
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PMID:Characterization of proteins by sequential isoelectric focusing on immobilized pH gradients and electrospray mass spectrometry. 852 1

The production of interleukin-6 (IL-6) in human gingival fibroblasts (Gin cells) is increased by lipopolysaccharide (LPS) from Campylobacter rectus (C. rectus), which is associated with adult periodontitis; however, the age-related changes in the susceptibility of Gin cells to C. rectus LPS remain unclear. We examined the influence of in vitro senescence on C. rectus LPS-stimulated IL-6 production in Gin cells. LPS was prepared from C. rectus ATCC 33238 using hot phenol-water. The Gin cells were established from healthy gingival tissue removed from three patients, aged 10-12 years. The cells were cultured until confluence then stimulated with LPS (0.01, 0.1, 1.0 and 10.0 micrograms/ml). Levels of IL-6 released in the medium were measured after incubation for 3, 6, 9, 12, and 24 h. In both young (5-6 population doublings) and senescent (17-20 population doublings) cells, LPS stimulated IL-6 production in a dose- and time-dependent manner. In response to 0.01-10.0 micrograms/ml of LPS, IL-6 production in the senescent cells was higher than that in the young cells. Using cells from each of the three donors, we found that this phenomenon of higher LPS-stimulated IL-6 production in senescent cells was reproducible. The greater capacity of the senescent cells to synthesize IL-6 in response to LPS was a higher production of mRNA for IL-6. This increase of IL-6 production induced by C. rectus LPS in senescent Gin cells could help to explain the increased susceptibility to periodontal diseases shown by aged individuals.
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PMID:In vitro senescence enhances IL-6 production in human gingival fibroblasts induced by lipopolysaccharide from Campylobacter rectus. 873 6

Three heteroglycans, T1a, T1b, and T1c, have been isolated from the body of Tremella fuciformis Berk. They are composed of mannose (Man), xylose (Xyl), glucose (Glc), fucose (Fuc), and glucuronic acid (GlcA). According to methylation analysis and partial acidic hydrolysis the main chains of T1a, T1b, and T1c consisted of (1-->3)-linked Man, which was branched at the 2, 4, or 6 positions. The branching points were linked with nonreducing terminal GIcA-residues or (1-->6)-linked glucan-chains. Molecular weights of the three heteroglycans are 53,000, 18,000, and 12,000 D respectively, but they undergo self-aggregation in water. T1a-T1c induce human monocytes to produce interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) in vitro. Acidic hydrolysate fractions of T1a (T1a-1, 2, 3, 4, 5) with molecular weight from 53,000 to 1,000 D, also induce human monocytes to produce IL-6 as efficient as T1a.
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PMID:Characterization and cytokine stimulating activities of heteroglycans from Tremella fuciformis. 879 58

Three different procedures were used to isolate lipopolysaccharides from the Salmonella enteritidis strain 477: phenol-water extraction with ethanol precipitation (LPS 1), phenol-water extraction with methanol precipitation (LPS 2) and FPLC purification (LPS 1/1). Production of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) was observed in the supernatants of adherent spleen cells of BALB/c mice after the stimulation and cultivation of the cells. The quantity of IL-1 beta and IL-6 depended on the method of LPS isolation. The highest level of IL-1 beta was recorded at LPS 2, and of IL-6 at the stimulation of cells by means of LPS 1.
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PMID:Production of IL-1 beta and IL-6 by adherent spleen cells after the stimulation with lipopolysaccharides from Salmonella enteritidis strain. 887 94

The effect of a prolonged low dose infusion of bacterial lipopolysaccharide (LPS) on acute phase-like reactions was examined in heifers. LPS (2 micrograms kg-1 dissolved in 100 ml water), or saline was infused (at 1 ml min-1) intravenously for 100 minutes and blood samples were taken at various times before, during and after the infusion. The serum concentrations of tumour necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and serum amyloid A (SAA) and the rectal temperature increased in response to the LPS infusion. Serum TNF alpha increased before the increases in IL-1 beta and IL-6 and remained high from 20 minutes after the onset of the infusion until the end of the sampling period (six hours). The LPS-induced increases in serum IL-1 beta and IL-6 were biphasic. Plasma cortisol and lactate concentrations also increased, and plasma glucose and beta-hydroxybutyrate concentrations decreased in response to the LPS infusion. The similarity of these reactions to changes observed in response to bacterial infections shows that the prolonged infusion of low doses of LPS is a good model for studying the acute phase response to Gram-negative bacterial infection in heifers.
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PMID:Characterisation of the acute phase response of heifers to a prolonged low dose infusion of lipopolysaccharide. 893 57


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