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)

Nitric oxide (NO) is an intercellular messenger molecule produced by a variety of cells, including macrophages. However, the role of NO in infection, especially its immunological role, is poorly understood. In the present study, the role of NO in Legionella pneumophila-infected macrophages was examined. Whereas infection of mouse macrophages in vitro with L. pneumophila did not induce detectable NO, when the macrophages were primed with interferon-gamma (IFN-gamma), the treated macrophages markedly inhibited bacterial replication and produced a large amount of NO. Treatment with NO inhibitors, such as NG-monomethyl-L-arginine (L-MMA) or aminoguanidine, as well as culture in arginine-free medium, significantly inhibited NO production; however, the anti-L. pneumophila activity induced by IFN-gamma was not diminished. Examination of cytokine levels in L. pneumophila-infected macrophages primed with IFN-gamma revealed a moderate increase of interleukin-6 (IL-6) production; however, inhibition of NO by L-MMA markedly increased IL-6 production. Reconstitution of NO in the L. pneumophila-infected macrophages primed with IFN-gamma and treated with L-MMA to inhibit endogenous NO production following addition of sodium nitroprusside reduced IL-6 production to normal levels. The levels of IL-6 mRNA in L-MMA-treated macrophages were the same as in nontreated macrophages, as demonstrated by quantitative RT-PCR. Thus, these results indicate that NO may regulate IL-6 production independently of its role in antimicrobial function in L. pneumophila-infected macrophages and their immunoregulation on IL-6 production may be due to a post-transcriptional mechanism.
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PMID:Immunoregulatory role of nitric oxide in Legionella pneumophila-infected macrophages. 880 92

The ability of dicatechol rooperol and esters to inhibit the production of cytokines in endotoxin-stimulated human alveolar macrophages, human blood monocyte/macrophages, histiocytic cell line U937, and rat alveolar macrophages was examined in vitro. Rooperol derivatives inhibited the production of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6. Of the esters tested on human cells, rooperol diacetate and tetraacetate were more potent inhibitors of cytokine production (IC50 in the range of 10-20 microM) than rooperol disulphate (IC50 in the range of 25-75 microM). The acetate esters also inhibited cytokine production in rat alveolar macrophages, whereas the sulphate had little effect. Rooperol and acetate esters, in the same concentration range, decreased the production of nitric oxide by rat alveolar macrophages stimulated by endotoxin. These concentrations of rooperol had no effect on cell viability, as indicated by incorporation of 14C-labelled leucine into macrophage proteins and their content of lactate dehydrogenase. The results obtained suggest that rooperol esters are potentially useful antiinflammatory agents.
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PMID:Cytokine production in human and rat macrophages and dicatechol rooperol and esters. 883 17

The effect of nitric oxide on the lipopolysaccharide (LPS)-induced cytokine production by alveolar macrophages was studied. When alveolar macrophages were cultured, substantial amounts of interleukin-1(IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha(TNF-alpha), and nitric oxide are produced upon stimulation with LPS. Inhibition of the nitric oxide production by the L-arginine analogue N(G)-monomethyl-L-arginine (NMMA), resulted in an increase of IL-1(beta) and IL-6, whereas the TNF-alpha concentrations remained unchanged, suggesting specific inhibitory effects of nitric oxide on the LPS-stimulated cytokine production by alveolar macrophages. The observed cytokine-modulation properties of nitric oxide did not result from cytotoxic actions of the oxidation of L-arginine on macrophages, since nitric oxide synthesis did not affect the viability of the alveolar macrophages. Conversely the nitric oxide donor S-nitroso-N-acetyl-D, L-penicillamine (SNAP) induced dose-dependent inhibition of IL-1 production in LPS-stimulated alveolar macrophages in which endogenous nitric oxide production was blocked. The results indicate that nitric oxide can affect the LPS-induced IL-1beta and IL-6 secretion by alveolar macrophages in an autoregulatory way and are discussed in view of the important physiologic consequences this autoregulation by nitric acid oxide may have.
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PMID:Alveolar macrophages autoregulate IL-1 and IL-6 production by endogenous nitric oxide. 884 78

To investigate the influence of inducible nitric oxide synthase on cerebral arteries after subarachnoid haemorrhage (SAH) in vivo, lipopolysaccharide (LPS), a major inducer of inducible nitric oxide synthase, was injected intracisternally into control and SAH model dogs. Intracisternal injection of LPS (0.5 mg) produced a long-lasting, submaximal vasodilation of the basilar artery of control dogs on angiography. This effect became significant at 4 hours after LPS injection and plateaued after 6 hours. This vasodilation was reduced by N(G)-monomethyl-L-arginine. Vasopressin slightly suppressed the vasodilation, while bradykinin increased it. The concentration of L-arginine in CSF decreased after LPS injection, while that of L-citrulline increased. In cytokines, the concentration of tumour necrosis factor-alpha; (TNF-alpha;) in CSF increased transiently at 4 hours after LPS injection, while interleukin-1 beta, interleukin-6, interferon-gamma, did not change. These data suggest that vasodilation by LPS is mainly due to nitric oxide predominantly synthesized by an inducible nitric oxide synthase, proximally induced by TNF-alpha. Our data make it unlikely that SAH itself induces the inducible nitric oxide synthase in vascular tissue, since isolated endothelium-denuded basilar artery from SAH model dogs did not respond to L-arginine. In SAH model dogs, the degree of vasodilation by LPS differed with the severity of vasospasm. Vasodilation was much greater in mild than in severe vasospasm in dogs, and was increased by superoxide dismutase. These findings suggest that the induction of inducible nitric oxide synthase or its activity may be less effective in severe vasospasm.
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PMID:Vasodilation by intrathecal lipopolysaccharide of the cerebral arteries after subarachnoid haemorrhage in dogs. 886 3

Recent work in many laboratories has revealed that cytokines are important mediators of inflammation, host defense, and tissue injury in a variety of neurological diseases. A role for astrocytes and microglia in these diseases has been considered pivotal, since both cell types readily produce and respond to cytokines in vitro and show morphologic and immunocytochemical evidence for activation in vivo. Although much of the work documenting these events has been generated in rodent systems, our laboratory has focused on human cell culture systems to define the nature of the activating signals for human microglia and astrocytes and their responses to activating cytokines and growth factors and evidence for activation. The results have shown that interleukin-1 (IL-1) is a potent activator of human astrocytes and induces cytokines such as tumor necrosis factor alpha and interleukin-6, and is a potent activator of nitric oxide generation in astrocytes. Astrocytes also promote microglial growth and differentiation through production of colony-stimulating factors, an activity that is enhanced following activation with IL-1. This review will summarize the human glia data generated in this and other laboratories and present hypotheses how glia may participate in certain human central nervous system diseases.
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PMID:Interleukin-1, nitric oxide and reactive astrocytes. 890 51

We investigated whether tolerance develops to the lipopolysaccharide-induced increase in vascular permeability of mouse skin on pretreatment with Salmonella typhimurium lipopolysaccharide. Lipopolysaccharide-induced plasma extravasation was assessed by determining Pontamine sky blue dye accumulation in the skin where lipopolysaccharide was injected s.c. 2 h previously. When mice were pretreated with lipopolysaccharide (0.15 mg/kg i.p.), the dye leakage induced by s.c. challenge with lipopolysaccharide (400 micrograms/site) was significantly, inhibited for 2-24 h after pretreatment, indicating the development of lipopolysaccharide tolerance. At 4 h after lipopolysaccharide (0.15 mg/kg i.p.), the dose-response curve of dye leakage against the challenge dose of lipopolysaccharide shifted about 2-fold to the higher dose. The dye leakage induced by lipopolysaccharide was inhibited by pretreatment with lipopolysaccharide in a dose-dependent manner (0.05-0.15 mg/kg i.p.). Lipopolysaccharide tolerance was not seen in adrenalectomized mice. When mice were pretreated with lipopolysaccharide and NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, at the same time, the hyporesponsiveness to lipopolysaccharide challenge disappeared. However, L-NAME was ineffective to inhibit the development of lipopolysaccharide tolerance when administered 24 h after lipopolysaccharide pretreatment or just before the lipopolysaccharide challenge. Tumor necrosis factor-alpha and interleukin-1 alpha but not interleukin-6 induced a similar hyporesponsiveness to lipopolysaccharide. These results suggest that tolerance develops to the lipopolysaccharide-induced increase in vascular permeability in mouse skin after a single lipopolysaccharide administration and that endogenous glucocorticoids and NO are necessary for induction of lipopolysaccharide tolerance. Hyporesponsiveness induced by lipopolysaccharide pretreatment may be mediated by production of some cytokines such as tumor necrosis factor-alpha or interleukin-1 alpha.
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PMID:Tolerance to lipopolysaccharide-induced increase in vascular permeability in mouse skin. 890 39

Endotoxic activities of lipopolysaccharide (LPS) isolated from Burkholderia (Pseudomonas) pseudomallei, a causative agent of melioidosis, were investigated. Compared to an enterobacterial LPS (SAE-LPS), B. pseudomallei LPS (BP-LPS) exhibited weaker pyrogenic activity in rabbits, lethal toxicity in galactosamine-sensitized mice and murine macrophage activation, i.e. production of tumor necrosis factor, interleukin-6 and nitric oxide. BP-LPS, on the other hand, exhibited stronger mitogenic activity to murine splenocytes than SAE-LPS; moreover, it stimulated even the splenocytes of LPS-resistant C3H/HeJ mice. Unusual chemical structures in the acid-stable inner core region attached to the lipid A moiety of BP-LPS may be responsible for this strong mitogenic activity.
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PMID:Biological activities of lipopolysaccharide of Burkholderia (Pseudomonas) pseudomallei. 893 61

Microcirculatory disturbances of the colon may contribute to the pathogenesis of inflammatory bowel disease. The aim of the study was to investigate the alterations of rectal blood perfusion in experimental colitis with reference to nitric oxide and heparin treatment. The study was carried out on 36 rats, divided into six groups: group I, control; group II, control + NG-nitro-L-arginine (L-NNA); group III, colitis without treatment; group IV, colitis + L-arginine; group V, colitis + L-NNA; group VI, colitis + heparin treatment. Experimental colitis was induced by 4% acetic acid enema, and 48 h after the enema, besides the measurement of rectal capillary blood flow by means of laser Doppler flowmetry, the serum interleukin-6 (IL-6) level and histopathological alterations within the rectal mucosa were examined. Experimental colitis resulted in a drop in rectal wall perfusion. L-Arginine and heparin treatment improved the microcirculatory values. The highest IL-6 level and the most advanced histopathological alterations were observed in the rats treated with L-NNA. L-Arginine treatment had no influence on IL-6 concentration, however it aggravated the inflammatory changes within the rectal mucosa. Heparin administration reduced the IL-6 values and also had a positive impact on the microscopic alterations within the rectal wall. It is concluded that heparin treatment has a beneficial effect on the microcirculatory disturbances and inflammatory changes observed in experimental colitis. The inhibition of nitric oxide-synthase aggravated the course of experimental colitis. L-Arginine administration improves the rectal blood flow but aggravates the histopathological alterations within the rectal wall.
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PMID:Is nitric oxide and heparin treatment justified in inflammatory bowel disease? An experimental study. 898 63

The role of Rel in the monocyte/macrophage lineage was examined in mice with an inactivated c-rel gene. Although the frequency of monocytic cells was normal in Rel-/- mice, we show that Rel serves distinct roles in regulating gene expression and immune effector function in different mature macrophage populations. Stimulated Rel-/- resident peritoneal macrophages produced higher than normal levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), but tumour necrosis factor-alpha (TNF-alpha) production was not induced. Diminished cytotoxic activity exhibited by resident Rel-/- macrophages was consistent with reduced nitric oxide production resulting from impaired up-regulation of inducible nitric oxide synthase expression. While a similar altered pattern of IL-6 and TNF-alpha expression was observed in stimulated Rel-/- peritoneal effusion macrophages, cytotoxic activity, nitric oxide, GM-CSF and G-CSF production by these cells was normal. The alternate regulation of certain genes in the two macrophage populations coincided with different patterns of nuclear Rel/NF-kappaB complexes expressed in normal resident and elicited cells. Collectively, these results establish that Rel is a positive or negative regulator of transcription in macrophages and that Rel has distinct roles in different macrophage populations.
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PMID:The Rel subunit of NF-kappaB-like transcription factors is a positive and negative regulator of macrophage gene expression: distinct roles for Rel in different macrophage populations. 900 85

Activated macrophages have been shown to exert cytostatic and cytotoxic effects toward tumor cells via nitric oxide (NO) release. In the CNS, microglial cells are considered to be the main resident population of immune effector cells. In this study, cytotoxic activity of N11, an immortalized murine microglial cell line, toward rat progressive DHD/PROb and regressive DHD/REGb colon carcinoma cells was examined in parallel with NO production. Cytotoxicity was evaluated using a novel method, the gamma-glutamyl transpeptidase (gamma-GTP) assay, based on the fact that DHD tumor cells expressed high levels of gamma-GTP activity, while no gamma-GTP activity was found in cells of the monocyte/macrophage lineage. Results showed that activation of N11 cells by interferon-gamma plus either lipopolysaccharide or tumor necrosis factor-alpha induced high amounts of NO release and cytotoxic effects toward DHD/PROb as well as DHD/REGb cells. NO release by activated N11 cells was augmented by addition of tumor cell-conditioned medium. Both NO release by N11 cells and cytotoxicity were blocked by addition of N(G)-monomethyl-L-arginine (L-NMA), an inhibitor of NO synthase, suggesting that cytotoxicity was mediated by N11-derived NO. However, in the presence of L-NMA an increased production of interleukin-6 was also observed. In conclusion, in opposition to information obtained with brain-derived endothelial cells, brain-derived microglial cells did not differentiate between progressive and regressive clones of colon carcinoma cells. Our results point to a specific role for both endothelial and microglial cell types in the context of brain metastasis. Microglial cells can be cytotoxic for tumor cells, and this cytotoxicity is mediated by NO.
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PMID:Microglial cells induce cytotoxic effects toward colon carcinoma cells: measurement of tumor cytotoxicity with a gamma-glutamyl transpeptidase assay. 900 56


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