UNIPROT:P05231 - FACTA Search

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Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin-1 (ET-1) is a vasoconstrictive peptide released by ischemic/injured endothelium which increases intracellular ionized calcium [Ca2+]i in vascular smooth muscle. Previous work from this lab has shown that ET-1 also increases human peripheral blood monocyte [Ca2+]i, and that 24 h incubation of monocytes with 10(-9) M ET-1 causes production of prostaglandin E2 and interleukin-6. In these studies, ET-1-stimulated monocyte supernatants were evaluated for their effect on neutrophil superoxide production. While ET-1 alone had no direct effect, incubation of neutrophils for 20 min in ET-1-stimulated monocyte supernatants resulted in a 10-fold increase in superoxide production over basal levels, 44% as much superoxide production as induced by peptide N-formyl-methionyl-leucyl-phenylalanine (N = 6, p < .001). Monocyte supernatants were analyzed for interleukin-8 (IL-8 or neutrophil activation protein) content by radioimmunoassay. ET-1-stimulation resulted in production of 54% as much IL-8 as lipopolysaccharide controls (N = 6, p < .001). While a number of monokines can activate neutrophils, IL-8 has been shown to be a potent neutrophil activator as well as a superoxide primer. Therefore, ET-1-treated monocytes probably upregulate neutrophil superoxide production via a mechanism which includes IL-8.
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PMID:Endothelin-stimulated monocyte supernatants enhance neutrophil superoxide production. 773 49

A replication-defective recombinant retrovirus containing the human papilloma virus E6/E7 genes (LXSN-16 E6E7) was used to immortalize stromal cells from human marrow. The E6/E7 gene products interfere with the function of tumor-suppressor proteins p53 and Rb, respectively, thereby preventing cell cycle arrest without causing significant transformation. Twenty-seven immortalized clones designated HS-1 to HS-27 were isolated, four of which are characterized in this report. Two cell lines, HS-5 and HS-21, appear to be fibroblastoid and secrete significant levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), macrophage-CSF (M-CSF), Kit ligand (KL), macrophage-inhibitory protein-1 alpha, interleukin-6 (IL-6), IL-8, and IL-11. However, only HS-5 supports proliferation of hematopoietic progenitor cells when cocultured in serum-deprived media with no exogenous factors. Conditioned media (CM) from HS-5 promotes growth of myeloid colonies to significantly greater extent than a cocktail of recombinant factors containing 10 ng/mL of IL-1, IL-3, IL-6, G-CSF, GM-CSF, and KL and 3 U of erythropoietin (Epo). Two additional clones, HS-23 and HS-27, resemble "blanket" cells, with an epithelioid morphology, and are much larger, broader, and flatter when compared with HS-5 and HS-21. These lines secrete low levels of growth factors and do not support proliferation of isolated progenitor cells in cocultures. CM from HS-23 and HS-27 also fail to support growth of myeloid colonies. Both HS-23 and HS-27 express relatively high levels of VCAM-1, yet HS-27 is the only line that supports the formation of "cobblestone" areas by isolated CD34+38lo cells. We hypothesize that HS-5, HS-21, HS-23, and HS-27 represent functionally distinct components of the marrow microenvironment.
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PMID:Functionally distinct human marrow stromal cell lines immortalized by transduction with the human papilloma virus E6/E7 genes. 784 21

Circulating levels of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in 13 children with autoimmune hepatitis (AIH) (seven with type 1 and six with type 2). In untreated children with type 1 AIH, TNF-alpha, IL-6, and IL-8 levels were elevated when compared to those of healthy controls (p < 0.005, p < 0.02, p = 0.06, respectively), whereas in children with type 2 AIH, cytokine levels were normal in all except one sample. A significant decrease in circulating IL-6, IL-8, and TNF-alpha was observed when patients were evaluated during a subsequent remission. We found no significant correlation of cytokine levels with alanine aminotransferase (ALT) activity, total serum gamma-globulins, or prothrombin activity. In patients with cirrhosis, serum IL-8 and IL-6 levels were higher (significantly in the case of IL-8) than those of patients without cirrhosis. In conclusion, activation of the in vivo production of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha appears to be associated with type 1 but not with type 2 AIH.
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PMID:Circulating levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in children with autoimmune hepatitis. 788 14

To determine the cytokine release during normothermic cardiopulmonary bypass, we have measured plasmatic levels of tumor necrosis factor-alpha and interleukins-1 beta, 6, and 8 in 10 patients during the first 24 hours after the start of bypass. Arterial blood samples were collected at intervals before, during, and after bypass. Interleukin-1 beta was not detectable in the plasma, and traces of tumor necrosis factor-alpha were detected in only three patients at times independent of the cardiopulmonary bypass procedure. Circulating endotoxin remained undetectable. Plasma interleukin-6 and interleukin-8 rose significantly from 2 until 24 hours after the start of bypass (p < 0.05) and peaked respectively at 4 and 2 hours after the beginning of bypass (interleukin-6, 268.1 +/- 131.43 pg/ml; interleukin-8, 370 +/- 420 pg/ml; mean peak +/- standard deviation). Peak values of interleukin-6 and interleukin-8 were correlated neither with the duration of aortic crossclamping or the bypass procedure nor with the hemodynamic parameters recorded at the same times. This study shows that normothermic cardiopulmonary bypass does not induce systemic release of tumor necrosis factor-alpha and interleukin-1 beta. A local production of these cytokines cannot be excluded, because interleukin-6 and interleukin-8 are produced by stimulated macrophages and monocytes in response to tumor necrosis factor-alpha and interleukin-1 beta. Our results, at normothermia, show a similar pattern of interleukin-6 and interleukin-8 release when compared with release during hypothermic cardiopulmonary bypass. Interleukin-8, an important chemotactic neutrophil factor, might play a role in reperfusion injuries observed in lungs and heart after cardiopulmonary bypass.
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PMID:Circulating cytokines in patients undergoing normothermic cardiopulmonary bypass. 793 96

Recent analysis of a various kinds of cytokines revealed that the cytokines are actively involved in a number of important biological functions including immunological and endocrine functions. The present study investigated the unique cytokine-mediated immunological and endocrinological functions in the intra-uterine space during pregnancy. A human placenta which expresses paternal and maternal antigens was revealed to escape from maternal immune systems by releasing immunosuppressive cytokines derived from the placenta. Placental cytokines such as interleukin-6 (IL-6) activated IL-6-receptor-mediated signal transduction pathways to produce human chorionic gonadotropin (hCG). IL-1 and tumor necrosis factor-alpha (TNF-alpha) synergistically augmented IL-6 production to stimulate hCG production. However, transforming growth factor-beta (TGF-beta) suppressed these cytokine-mediated hCG production as well as IL-6 production. Thus, these placental cytokines, mainly derived from trophoblasts, cooperatively contributed to hCG production. IL-8 and monocyte chemotactic and activating factor (MCAF) activate host defense mechanism by activating neutrophils and monocytes as well as macrophages, respectively. IL-6 also activates immune responses and promote synthesis of acute-phase reactant proteins, contributing to augmentation of host defense mechanism in a different way from IL-8 and MCAF. Human placenta in the 3rd trimester actively produced these cytokines for potentiation of placental defense mechanism during pregnancy and in chorioamnionitis. A fetus in chorioamnionitis also produced these cytokines in utero for potentiation of fetal defense mechanism. Among these cytokines, IL-8 in a cord serum was a very sensitive and useful marker for clinical diagnosis of chorioamnionitis. Cord serum IL-6, in contrast, stimulated the synthesis of surfactant protein-A (SP-A) to promote fetal lung maturation and reduce the incidence of RDS. Collectively, the present study revealed the cytokine network in the placenta regulating maternal immune responses, placental endocrine functions, feto-maternal defense mechanism and fetal respiratory maturation.
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PMID:[Immunological analysis of the mechanism of maternal tolerance of a fetus and the cytokine-mediated regulation of feto-placental functions]. 808 6

Chronic airway inflammation is an important feature of cystic fibrosis (CF), markedly influencing morbidity and mortality. We wanted to assess the contribution of the respiratory epithelium in the mediation of local inflammatory events, and, more particularly, its regulating role through cytokine secretion. We have studied the regulation of interleukin-6 and 8 (IL-6 and IL-8) production by the SV40 transformed airway epithelial cell line JME/CF15 (homozygous for the deletion of Phe 508). We show that unstimulated JME/CF15 cells secrete IL-6 and IL-8. Neutrophil chemotactic activity (NCA) is detected in supernatants. The secretion of IL-6 and IL-8 is increased following stimulation of the JME/CF15 cells by IL-1 beta and neutrophil elastase. Lipopolysaccharide and granulocyte macrophage colony stimulating factor (GM-CSF) have no effect on secretion of IL-6 or IL-8. Neutrophil elastase inactivates recombinant human IL-6 at 37 degrees C in vitro, but has no effect at 4 degrees C, suggesting a proteolytic effect of elastase on IL-6. IL-8 activity remains preserved, even after prolonged exposure to elastase. Our data suggest that the airway epithelium may play an active role in the mediation of neutrophil chemotaxis. Local production of IL-8 in response to elastase and IL-1 beta, together with the inactivation of the anti-inflammatory protein IL-6, may result in a significant upregulation of airway inflammation in cystic fibrosis.
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PMID:Regulation of cytokine secretion by cystic fibrosis airway epithelial cells. 811 34

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) has potent antipyretic and antiinflammatory properties. When administered systemically, the naturally occurring molecule and its COOH-terminal tripeptide sequence inhibit inflammation induced by peripherally applied irritants and intradermal injections of mediators of inflammation such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha). We recently found that alpha-MSH can act solely within the brain to inhibit inflammation caused by a general irritant applied to the skin. This activity appears to be shared with salicylate drugs and the combined observations suggest the existence of descending neurogenic antiinflammatory signals capable of modulating inflammation in peripheral tissues. To improve our knowledge of the scope of this action of the peptide, alpha-MSH was injected into the cerebral ventricles (i.c.v.) of mice that had received intradermal injections in the ear of mediators of inflammation: IL-1 beta, IL-8, leukotriene B4, and platelet-activating factor. The centrally administered peptide inhibited the actions of all of these proinflammatory agents as determined from comparisons with measures of ear edema over time in control animals; this indicates that the central peptide can alter inflammation induced in the periphery by major mediators of inflammation. In tests confined to IL-1 beta, central administration of alpha-MSH(11-13) was also effective. These findings support the concept of a descending neurogenic antiinflammatory influence promoted by an action of alpha-MSH within the brain, an inhibitory influence that is not restricted to modulation of just one or a limited set of the mediators of inflammation.
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PMID:Central neurogenic antiinflammatory action of alpha-MSH: modulation of peripheral inflammation induced by cytokines and other mediators of inflammation. 812 2

The basophilic leukaemia cell line KU812 can be induced to differentiate into basophil-like cells in vitro when exposed to supernatant from the Mo T-cell line. KU812 cells express affinity receptors for IgE, produce histamine and tryptase and have the capacity for IgE-mediated histamine release. In this study we have examined the cytokines, produced by the Mo cell line, which are responsible for the observed differentiation-inducing effect in the KU812 cell line. It was shown that interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) induced differentiation in the KU812 cells and that these cytokines were responsible for the differentiation-inducing effect of the Mo supernatant. Other cytokines tested, IL-1 beta, IL-2, IL-4, IL-5, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and nerve growth factor (NGF) were without effect on the KU812 cells. KU812 was also shown to express receptors for both TNF-alpha and IL-6 after 3 days cultivation with conditioned media from the Mo T-cell line. Untreated cells showed no detectable levels of TNF-alpha or IL-6 receptors indicating induction of these receptors during differentiation. Spontaneous differentiation was shown to occur under serum-free conditions which may be the result of endogenous IL-6 production through an autocrine loop. The activity of TNF-alpha and IL-6 could be blocked by specific monoclonal antibodies (mAb) to the respective cytokine.
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PMID:TNF-alpha and IL-6 induce differentiation in the human basophilic leukaemia cell line KU812. 813 23

Studies were carried out on some biological activities of Helicobacter pylori porins in vitro. We extracted and purified a porin with an apparent molecular mass of 30 kDa. Human polymorphonuclear leukocytes preincubated with H. pylori porins showed a decrease of chemotaxis, of adherence to nylon wool, and of chemiluminescence. Used as chemotaxins in place of zymosan-activated serum or as chemotaxinogens in place of zymosan, the porins induced polymorphonuclear leukocyte migration. Human monocytes and lymphocytes cultivated in the presence of H. pylori porins released cytokines. Release of the various cytokines studied was obtained with differentiated kinetics and at various porin concentrations. Starting only 3 h after culture, tumor necrosis factor alpha is released quickly, reaching a peak at 18 h, at a porin concentration of 1 microgram/ml/10(6) cells. Interleukin-6 (IL-6) appears later, with a peak at 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells. Lymphocytes stimulated by H. pylori porins release gamma interferon after 18 h of culture at higher concentrations of porins (20 micrograms/ml/10(6) cells). Granulocyte macrophage colony-stimulating factor is released from 6 to 48 h at a concentration of 1 microgram/ml/10(6) cells, while both IL-3 and IL-4 are released after 18 h of culture at different porin concentrations (0.1 and 1 microgram/ml/10(6) cells, respectively). Our results lead us to think that during H. pylori infection, surface components, porins in particular, are able to induce a series of chain reactions ranging from the inflammatory to the immunological responses.
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PMID:Immunobiological activities of Helicobacter pylori porins. 813 46

To explore the pathogenic mechanisms involved in adenovirus infection, we evaluated total levels of immunoglobulins, antiadenovirus antibodies, adenovirus-specific circulating immune complexes, and cytokines in serum samples obtained from 38 hospitalized children with adenovirus infection. According to their clinical findings and outcome, the infections were classified as follows: (1) moderate (group I, n = 10), (2) severe (group II, n = 12), and (3) fatal (group III, n = 16). About 60% of the children had elevated IgM levels. IgG-containing adenovirus-specific circulating immune complexes were initially detected in 7 of 16 group III patients, 4 of whom had low serum levels of the third component of complement. A decrease in initial antiadenovirus IgG antibodies was observed in 3 of 10 patients in group III. Serum interleukin-6 was not detected in group I (none of 10), but was present in group II (7 of 12, p = 0.016) and group III (13 of 16, p < 0.001). Interleukin-8 was detected in all groups; values in fatal cases were significantly higher than in surviving children. Tumor necrosis factor alpha was not observed in group I (none of 10) and was uncommon in group II (2 of 12) but was frequently detected in group III (9 of 15, p = 0.01). Interleukin-1 and interleukin-4 were rarely detected in serum samples. Increased concentrations of interleukin-6, interleukin-8, and tumor necrosis factor alpha were associated with hypoperfusion, febrile peaks, tonic-clonic seizures, and septic shock. In 5 of 10 patients in groups II and III, autoantibodies specific for smooth muscle were found. Our findings indicate that high serum values for interleukin-6, interleukin-8, and tumor necrosis factor alpha are associated with severity of adenovirus infection.
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PMID:Cytokines in adenoviral disease in children: association of interleukin-6, interleukin-8, and tumor necrosis factor alpha levels with clinical outcome. 817 57

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