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)

Comparison was made between the immunobiological and antigenic properties of two lipoteichoic acid (LTA) fractions (LTA-1 and -2) from Enterococcus hirae ATCC 9790, their glycolipid portions, and synthetic compounds partially mimicking the above bacterial products. The more lipophilic LTA-2 fraction was capable of inducing serum tumor necrosis factor alpha and interleukin-6 in muramyldipeptide-primed mice and serum gamma interferon in those primed with Propionibacterium acnes. The LTA-2 fraction also induced tumor necrosis factor alpha, interleukin-6, and thymocyte-activating factor (essentially interleukin-1) in murine peritoneal macrophage cultures. Consecutive intravenous injections of muramyldipeptide and the LTA-2 fraction in Meth A fibrosarcoma-bearing BALB/c mice caused hemorrhagic necrosis and marked regression leading to complete regression of the tumor with no accompanying weakening or lethal effects. The LTA-2 fraction was at least 10,000-fold less pyrogenic in rabbits than a reference endotoxic lipopolysaccharide. The more hydrophilic LTA-1 fraction, on the other hand, showed at most marginal activity in the in vivo and in vitro assays. Natural glycolipids (NGL-1 and -2) which were prepared from a chloroform-methanol extract of Streptococcus pyogenes and E. hirae cells, and comparable in structure to the lipid moieties of the LTA-1 and -2 fractions, respectively, were practically inactive in all of the assays. None of the test synthetic compounds was immunobiologically active, although synthetic partial counterparts of the structure of LTA proposed by W. Fischer (Handb. Lipid Res. 6:123-234, 1990) reacted with murine monoclonal antibody TS-2, which was raised against OK-432, a penicillin-killed S. pyogenes preparation, and capable of neutralizing the cytokine-inducing activities of the LTA-2 fraction.
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PMID:Molecular and structural requirements of a lipoteichoic acid from Enterococcus hirae ATCC 9790 for cytokine-inducing, antitumor, and antigenic activities. 780 84

A variety of preparations of Tripterygium wilfordii Hook.F (TWHF) have been reported to be effective in the treatment of autoimmune diseases, including a chloroform methanol extract termed T2 and an ethyl acetate (EA) extract. The immunosuppressive activity of the EA extract was analyzed and the components accounting for this effect determined and compared to those of T2. More than 0.25 microgram/ml of the EA extract inhibited antigen- and mitogen-stimulated human T cell proliferation. The inhibitory effect of the EA extract on T cell proliferation resulted largely from suppression of interleukin-2 production. At concentrations that inhibited T cell function, the EA extract also profoundly suppressed [3H]-thymidine incorporation by mitogen-stimulated B cells, but it did not inhibit antigen presentation by monocytes and only modestly affected interleukin-6 production by lipopolysaccharide-stimulated monocytes. The profile of inhibition was comparable to that previously reported for the chloroform-methanol extract of Tripterygium wilfordii Hook.F, T2. To delineate the components of these extracts that might account for their immunosuppressive effect, we analyzed the composition of diterpenoid compounds. Both extracts contained triptolide and tripdiolide as the major immunosuppressive diterpenoids, but at different concentrations. Comparison of the composition of these extracts and the inhibitory capacity of the purified components indicated that the triptolide concentration of the EA extract can account for its immunosuppressive activity, although the combination of both triptolide and tripdiolide or other unknown components may be necessary to explain the inhibitory effects of T2.
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PMID:The identity of immunosuppressive components of the ethyl acetate extract and chloroform methanol extract (T2) of Tripterygium wilfordii Hook. F. 789 48

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

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

In the hope of identifying agents of therapeutic value in immunoglobulin A nephropathy (IgA-N), we tested crude methanol extracts of 15 Chinese herbs for their effect on human mesangial cel proliferation in vitro. The results indicated that 7 out of the 15 crude extracts inhibited human mesangial cell proliferation activated by interleukin-1beta and interleukin-6. The extracts and their median inhibitory concentrations were as follows (in microg/ml): Selaginella tamariscina (MLS-032), 56.0 +/- 2.0; Ixeris chinensis (MLS-033), 62.7 +/- 1.7; Polygonum hypoleucum Ohwi (MLS-034), 25.0 +/- 1.5; Scutellaris rivularis (MLS-036), 39.6 +/- 1.1; Condonacanthus paucifiorus (MLS-042),63.6 +/- 2.6; Xanthium strumarium (MLS-043), 42.8 +/- 1.3; Daemonoropus margaritae (MLS-044), 56.1 +/- 1.9. These findings indicate that human mesangial cells were most sensitive to MLS-034 treatment. These herbs also decreased interleukin-1beta and tumor necrosis factor-alpha production. Moreover, TNF-alpha mRNA expression was inhibited by MLS-034. It is unlikely that cytotoxicity was involved, because no cell deaths were observable. We hypothesize that the inhibitory mechanisms of these Chinese herbs may be related to the impairments of gene expression and production of cytokines in human mesangial cells. Plans are underway for the isolation of pure compounds from these Chinese herbs and the elucidation of their mechanisms of action.
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PMID:Chinese herbs as modulators of human mesangial cell proliferation: preliminary studies. 966 76

Interleukin-2 and interleukin-6 can stimulate the growth and proliferation of T lymphocytes and the differentiation of activated B lymphocytes respectively, and in turn enhance cellular and humoral immune responses. In this work, an expression clone using Pichia pastoris, a methylotrophic yeast strain, has been developed in order to produce large amounts of the functional recombinant fusion protein pIL-6-IL-2, which contains the mature porcine interleukin-6 peptide and the mature porcine interleukin-2 peptide. Two components of the fusion protein were connected by means of a flexible linker (Gly-Gly-Gly-Gly-Ser-Glu-Phe-Gly-Ser-Gly-Gly). In response to 1% methanol induction, the recombinant strain GS115\9K-IL6-IL2 secreted an exogenous protein, with a molecular weight of approximately 40 kD, into the culture medium. This was confirmed to be pIL-6-IL-2 by means of SDS-PAGE and Western Blot analysis. The protein was visible on the 2nd day following methanol induction, and peaked on the 4th day. By this time, the level had reached 50 mg\L as determined using the method of Bradford. After treatment with PNGase F and analysis of the concentration of sugar, the fusion protein pIL-6-IL-2 was further confirmed to be mainly a glycoprotein with an approximately 2 kDa sugar decoration. In addition, the IL-6 and IL-2 biological activities of the fusion protein, determined by cell proliferation assays using the IL6-dependent cell line B9 and the IL2-dependent cell line CTLL-2, reached 1 x 10(5) U\mg and 8 x 10(5) U\mg, respectively. This report is the first description of fused porcine cytokines expressed in P. pastoris, which might be an interesting adjuvant product for veterinary vaccines.
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PMID:Expression of an interleukin-6 - interleukin-2 fusion protein (pIL-6-IL-2) in P. pastoris. 1554 49

As a kind of pleiotropic cytokine, Interleukin-6 (IL-6) becomes more and more popular in the fields of disease diagnosis and candidate adjuvants. In this study, the porcine Interleukin-6 (pIL-6) cDNAs un-coding signal peptides was cloned into pPIC9K (the expression vector of Pichia pastoris) to construct the pPIC9K-IL6, which was further transformed into P. pastoris GS115 strain. After being induced by 1% methanol, the recombinant strain excreted a protein in supernate of culture, with molecular weight of 24.5KD approximately, which was proved to be pIL6 through SDS-PAGE and western blotting. This P. pastoris product wasn't modified by N-hyperglycosylation. After purified, pIL-6 could reach to 8 x 10(4) IU/mg of bioactivity unit by the cell proliferation of B9 assay. Through researching the characters of the recombinant protein pIL6, we have made a great progress on the study of rpIL6 as veterinary vaccine's adjuvant.
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PMID:[Expression of porcine interleukin-6 in Pichia pastoris]. 1598 32

Opuntia humifusa Raf. (O. humifusa Raf.) is a member of the Cactaceae family. To determine the antioxidative and anti-inflammatory effects of this herb, various solvent fractions (methanol, hexane, chloroform, ethyl acetate, butanol, and water) prepared from the leaves of cacti were tested using DPPH (2,2-diphenyl-l-picrylhydrazyl radical) and xanthine oxidase assays, and nitric oxide (NO)-producing macrophage cells. We found that O. humifusa Raf. displayed potent antioxidative and anti-inflammatory activity. Thus, all solvent fractions, except for the water layer, showed potent scavenging effects. The scavenging effect of the ethyl acetate fraction was higher than that of the other fractions, with IC50 values of 3.6 and 48.2 microg mL(-1). According to activity-guided fractionation, one of the active radical scavenging principles in the ethyl acetate fraction was found to be quercetin. In contrast, only two fractions (chloroform and ethyl acetate) significantly suppressed nitric oxide production from the lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, chloroform and ethyl acetate fractions significantly blocked the expression of inducible nitric oxide synthetase (iNOS) and interleukin-6 (IL-6) from the RAW264.7 cells stimulated by LPS. Moreover, ethyl acetate fractions significantly blocked the expression of IL-1beta from the RAW264.7 cells stimulated by LPS. Therefore, the results suggested that O. humifusa Raf. may modulate radical-induced toxicity via both direct scavenging activity and the inhibition of reactive species generation, and the modulation of the expression of inflammatory cytokines. Finally, O. humifusa Raf. may be useful as a functional food or drug against reactive species-mediated disease.
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PMID:Radical scavenging and anti-inflammatory activity of extracts from Opuntia humifusa Raf. 1639 71

The present study is part of a large-scale investigation of the antitumor effects of Biophytum sensitivum on B16F-10 melanoma cells. The investigation involved the regulatory effect of B sensitivum on nitric oxide and cytokine production in B16F-10 cells, tumor-associated macrophages, and peritoneal macrophages as well as on the apoptotic process in B16F-10 melanoma cells. B sensitivum at a concentration of 10 microg/mL could significantly (P< .001) inhibit production of nitric oxide and proinflammatory cytokines such as interleukin-1beta, interleukin-6, granulocyte monocyte-colony stimulating factor, and tumor necrosis factor-alpha in B16F-10 cells, tumor-associated macrophages, and peritoneal macrophages. Incubation of B16F-10 cells with B sensitivum showed the presence of apoptotic bodies and induced DNA fragmentation. Furthermore, B sensitivum showed an inhibitory effect on inducible nitric oxide synthase as well as bcl-2 expression, and up-regulated p53 and caspase-3 messenger RNA expression in B16F-10 melanoma cells. The observed results suggest that regulation of proinflammatory cytokine production by tumor cells, tumor-associated macrophages, and resident macrophages accompanied by altered inducible nitric oxide synthase, bcl-2, caspase-3, and p53 messenger RNA expression by B sensitivum methanol extract induces apoptosis in B16F-10 melanoma cells.
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PMID:Apoptotic effect of Biophytum sensitivum on B16F-10 cells and its regulatory effects on nitric oxide and cytokine production on tumor-associated macrophages. 1804 85

In this study, we investigated the effect of the methanol extract of fruits of Vitis amurensis Rupr. (Vitaceae; MEVA) on the mast cell-mediated allergy model and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases, such as asthma and sinusitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. MEVA inhibited compound 48/80-induced systemic reactions and serum histamine release in a dose-dependent manner in mice. MEVA decreased immunoglobulin E (IgE)-mediated local allergic reactions, passive cutaneous anaphylaxis. MEVA dose-dependently reduced histamine release from mast cells activated by compound 48/80 or IgE. The inhibitory effect of MEVA on histamine release was mediated by the modulation of intracellular calcium. In addition, MEVA attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated secretion of tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-8 in human mast cells. The inhibitory effect of MEVA on these proinflammatory cytokines was p38 mitogen-activated protein kinase and nuclear factor-kappaB (NF-kappaB) dependent. Our findings provide evidence that MEVA inhibits mast cell-derived, immediate-type allergic reactions and involvement of proinflammatory cytokines, p38 MAPK, and NF-kappaB in these effects.
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PMID:Antiallergic effects of Vitis amurensis on mast cell-mediated allergy model. 1822 74


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