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

Recombinant growth factors and proinflammatory cytokines were added to primary cultures of human intrahepatic biliary duct epithelia to test for their ability to stimulate DNA synthesis and elicit cytokine production. Interleukin-6 and hepatocyte and epidermal growth factors were found to increase the DNA labeling index of biliary duct epithelium from fourfold to sixfold 24 hr after their addition to primary biliary duct epithelium cultures maintained in serum-free medium. The proliferative responses to all three biliary duct epithelium mitogens peaked within 24 hr, and hepatocyte growth factor was effective over a concentration range of 1.0 to 50 ng/ml, whereas interleukin-6 was effective from 1 to 1,000 U/ml. Insulin-like growth factor, phorbol myristate acetate, interleukin-1 beta and platelet-derived growth factor BB showed mild stimulatory effects, whereas interleukin-4, gamma-interferon, phytohemagglutinin and platelet-derived growth factors AA and AB did not increase DNA synthesis in biliary duct epithelium. Interleukin-1 beta and phorbol myristate acetate were also shown to induce in a dose-dependent fashion a threefold to fivefold increase of interleukin-6 production as measured by enzyme-linked immunosorbent assay in human primary biliary duct epithelium cultures, when compared with hepatocyte growth factor, epidermal growth factor, insulin-like growth factor, phytohemagglutinin, tumor necrosis factor-alpha or platelet-derived growth factor. These results show that interleukin-6 participates in growth regulation of human biliary duct epithelium. This could be exerted in a paracrine or autocrine manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human biliary epithelial cells secrete and respond to cytokines and hepatocyte growth factors in vitro: interleukin-6, hepatocyte growth factor and epidermal growth factor promote DNA synthesis in vitro. 804 98

Cell cultures of primary mouse granulosa cells were transfected with a v-myc-containing plasmid, and the resulting stable cell lines were tested for their steroidogenic properties and physiologic status. Granulosa cells were obtained from 22-day-old NMRI mice injected with 8 IU pregnant mare serum gonadotropin i.p. 2 days earlier. In Passage 1 the cells were transfected with pSVv-myc using calcium phosphate precipitation or lipofectin. The 3 beta- and 17 beta-hydroxy steroid dehydrogenase activity was visualized in control cultures. The three cell lines obtained have been in culture for over 1 yr and have been subcultured for more than 90 passages. The cell line GRM01, with a doubling time of 37 +/- 3 h and a diploid modal chromosome number, produced progesterone, estradiol, as well as inhibinlike and activinlike material under basal conditions. A combination of follicle-stimulating hormone and luteinizing hormone was able to increase the secretion of progesterone. GRM01L, a fast growing clone of the GRM01 line with a doubling time of 10 +/- 1 h, retained only the capacity to produce activinlike material and transforming growth factor-beta, and it was the only one with a tumorigenic capacity. Epidermal growth factor, insulin, and interleukin-6 were able to induce the [3H]thymidine incorporation into DNA in these two cell lines. GRM02, with a doubling time of 36 +/- 2 h and a hypertriploid modal chromosome number, produced progesterone and activinlike and inhibinlike material. Follicle-stimulating hormone and luteinizing hormone were able to enhance the secretion of progesterone. For this cell line, only insulin was shown to induce [3H]thymidine incorporation into DNA.
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PMID:Characterization of immortalized mouse granulosa cell lines. 816

The islet from human fetal pancreas was separated by collagenase type V (0.5 mg/ml) and cultured to observe spontaneous secretion of interleukin-6 (IL-6), its relationship to insulin secretion, regulatory effect of IL-6 on insulin secretion of islets and IL-6 gene expression of human fetal islets. IL-6 was secreted by cultured human fetal islets in vitro and paralleled to their insulin secretion. The MH60.BSF2 cell proliferated by 50 folds when cultured to the supernatant of human fetal islets. RNA dot hybridization with bioting-labelled IL-6 cDNA showed that IL-6 gene expressed on human fetal islets. IL-6 promoted the insulin secretion of islets dose-dependently. The results suggested that IL-6 may be one of the promoting or regulating factors in the insulin secretion of islets.
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PMID:[Interleukin-6 gene expression of human fetal islets and its relation to insulin secretion]. 831 93

Human thymic epithelial cells (TEC) of medullary phenotype were cultured for 14 days in a growth factor-defined serum-free medium. The effects of added growth factors on cell numbers and the production of cytokines were investigated by separate exclusion of the various growth factors from the medium. We found that hydrocortisone stimulated cell proliferation but inhibited the differentiation of TEC and significantly reduced the production of interleukin-1 alpha, interleukin-6 and granulocyte-macrophage colony stimulating factor. Insulin was found to enhance the differentiation of TEC and the production of the three cytokines. Transferrin and choleratoxin were found to inhibit cell proliferation, but they did not affect production of the cytokines. Exclusion of epidermal growth factor, however, leads to cell death. We conclude that it is essential to exclude hydrocortisone from the medium to optimize production of cytokines, and that transferrin and choleratoxin seem to be unnecessary constituents in serum-free cultures of human TEC.
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PMID:Effects of growth factors on cytokine production in serum-free cultures of human thymic epithelial cells. 835 99

The regulation of metallothionein induction in cultured rat hepatocytes was investigated with Zn, hormones, cytokines and either the synthetic glucocorticoid, dexamethasone, or the endogenous rat glucocorticoid, corticosterone. A concentration-dependent increase was seen with Zn (two- to fivefold increase in 24 h, Zn 10-50 mumol/L). Dexamethasone at 1 mumol/L increased metallothionein synthesis by fourfold that of the controls. Maximal metallothionein concentrations of 17-fold the control value were seen with 50 mumol/L Zn and 1 mumol/L dexamethasone. Interleukin-6 (1 x 10(5) U/L) alone did not induce metallothionein but increased it 35-65% with Zn+dexamethasone. Like dexamethasone, corticosterone had a dose dependent effect on metallothionein and synergy with Zn and Zn+interleukin-6. Dexamethasone was approximately 100 times more potent than corticosterone at 10-100 mumol/L. Physiological concentrations of corticosterone (1 mumol/L) when added alone, with Zn (10 mumol/L), and with Zn+interleukin-6 resulted in inductions of 2.2, 5.0 and 7.4-fold above the control cultures. Glucagon (1 mumol/L) had no independent effect but increased metallothionein by 31% and 33% with Zn(10 mumol/L)+dexamethasone (1 mumol/L) and Zn-dexamethasone+interleukin-6, respectively. There was no accumulation of metallothionein with interleukin-1 beta, tumor necrosis factor alpha or interferon gamma (1 x 10(5) U/L) alone, but interleukin-1 beta and tumor necrosis factor alpha enhanced the response obtained with Zn+dexamethasone with and without interleukin-6. Insulin (100 U/L) alone, caused metallothionein accumulation and further enhanced the response seen with Zn+dexamethasone+interleukin-6+glucagon. No additional enhancement was seen with interleukin 1 beta+tumor necrosis factor alpha+interferon. The results demonstrate that concentrations of corticosterone in rats with experimental inflammation facilitate metallothionein induction with Zn and interleukin-6.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Corticosterone enhances the zinc and interleukin-6-mediated induction of metallothionein in cultured rat hepatocytes. 836 Jul 72

The non-obese diabetic (NOD) mouse is a spontaneous model of human insulin-dependent diabetes mellitus. Both CD4+ and CD8+ T cells infiltrate the pancreatic islets of NOD mice prior to beta-cell destruction. T-cell lines isolated from the islets of NOD mice are tools for studying the pathogenesis of insulin-dependent diabetes mellitus. During attempts to generate such lines we isolated an autoreactive CD4+ T-cell line, designated C2, from the 'insulitis' lesion of a 20-week-old female non-diabetic NOD/WEHI mouse. Islet T cells were propagated by the addition of interleukin-2 and reexposure every 2 weeks to whole NOD islets and irradiated NOD spleen cells as antigen presenting cells. C2 cells proliferated up to 100-fold upon exposure to NOD antigen presenting cells but did not respond to whole NOD islets or antigen presenting cells from allogeneic mouse strains. Proliferation of C2 cells to NOD antigen presenting cells was blocked by a monoclonal antibody against the unique class II MHC molecule of NOD, I-Ag7. In response to NOD antigen presenting cells, C2 cells secreted interferon-gamma, tumour necrosis factor-alpha and interleukin-6 but no detectable interleukin-2, interleukin-4 or interleukin-10, a pattern of cytokine secretion more characteristic of Th1 CD4 cells. C2 cells displayed significant cytotoxicity in a redirected lysis assay. To explore a possible role for autoreactive T cells in the pathogenesis of autoimmune diabetes, C2 cells were injected i.v. into female NOD mice that had received cyclophosphamide to accelerate development of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppression of diabetes mellitus in the non-obese diabetic (NOD) mouse by an autoreactive (anti-I-Ag7) islet-derived CD4+ T-cell line. 840 38

The in vitro production of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) by monocytes was examined in patients with insulin-dependent diabetes mellitus (IDDM), in those with noninsulin-dependent diabetes mellitus (NIDDM), and in healthy volunteers. The production of IL-1 and IL-6 by monocytes was significantly lower in IDDM patients than in NIDDM patients and normal subjects whereas the TNF-alpha production by monocytes did not differ between IDDM patients and normal subjects. On the other hand, the TNF-alpha production was significantly higher in NIDDM patients than in IDDM patients and normal subjects. There was a significant correlation between IL-1 and IL-6 concentrations in culture supernatants of monocytes for IDDM patients but not for NIDDM patients and normal subjects. Neither glucose nor insulin showed any stimulatory effect on in vitro production of these monokines. In the serial observation lasting 3-18 months, the monocyte production of IL-1 was found to be consistently reduced in IDDM patients unrelated to the control state of diabetes, suggesting that the reduction of the IL-1 and IL-6 production by monocytes in IDDM patients may be intrinsically affected by immunological defects.
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PMID:In vitro production of interleukin-1, interleukin-6, and tumor necrosis factor-alpha in insulin-dependent diabetes mellitus. 840 55

The effects of inflammatory cytokines (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha) on energy metabolism were studied in primary cultured rat hepatocytes. Adenine nucleotide (ATP, ADP, and AMP) content, lactate production, the ketone body ratio (acetoacetate/beta-hydroxybutyrate) reflecting the liver mitochondrial redox state (NAD+/NADH), and nitric oxide formation were measured. Insulin increased ATP content in hepatocytes and had a maximal effect after 8-12 h of culture. Both interleukin-1beta and interleukin-6, but not tumor necrosis factor-alpha, significantly inhibited the ATP increase time- and dose-dependently. Interleukin-1beta and interleukin-6 also stimulated lactate production. During the same period, interleukin-1beta but not interleukin-6 decreased the ketone body ratio. Furthermore, interleukin-1beta markedly stimulated nitric oxide formation in hepatocytes, and this increase was blocked by NG-monomethyl-L-arginine (a nitric oxide synthase inhibitor) and by interleukin-1 receptor antagonist. NG-monomethyl-L-arginine reversed inhibition of the ATP increase, decrease in the ketone body ratio, and increase in lactate production, which were induced by interleukin-1beta. Interleukin-1 receptor antagonist completely abolished all of the effects induced by interleukin-1beta. These results demonstrated that interleukin-1beta and interleukin-6 affect the insulin-induced energy metabolism in rat hepatocytes by different mechanisms. Specifically, interleukin-1beta inhibits ATP synthesis by causing the mitochondrial dysfunction, a process which may be mediated by nitric oxide.
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PMID:Regulation of energy metabolism by interleukin-1beta, but not by interleukin-6, is mediated by nitric oxide in primary cultured rat hepatocytes. 860 98

To study the effect of interleukin-6 (IL-6) on glucose transport, 2-deoxy-D-glucose (2-DOG) uptake in 3T3-L1 adipocytes after incubation with IL-6 was measured. IL-6 increased 2-DOG uptake maximally after 5 hours by 30 +/- 12%, with a half-maximal effect at an IL-6 concentration of approximately 800 U/mL. 3-O-methylglucose uptake was stimulated in a similar way, indicating that IL-6 enhanced glucose transport rather than phosphorylation. IL-6-induced glucose transport was additive to the effect of insulin. Addition of cycloheximide did not affect the stimulatory action of IL-6, although cycloheximide itself had profound effects on basal glucose transport. We conclude that IL-6 may enhance glucose uptake by increasing GLUT-1 intrinsic activity.
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PMID:Interleukin-6 enhances glucose transport in 3T3-L1 adipocytes. 864 90

Various plasma protein patterns following inflammation and metabolic stress were described since diagnostic value of ESR was established. This reactive dysproteinemia is now recognized to reflect the shift in hepatic proteosynthesis after the immunoendocrinological activation. Four main groups of mediators are necessary for expression of hepatic positive and negative acute phase proteins (APPs): first and second "wave' of proinflammatory cytokines, further glucocorticoids and growth factors including insulin. Actual data showing details of the immunological and endocrinological regulation of stress hepatocyte proteosynthesis are summarized and our own results are presented. We evaluated the diagnostic use of APPs in some defined clinical situations (neutropenic period after bone marrow transplantation, postoperative complications) and correlated APPs with the plasma levels of the circulating interleukin-6 and cortisol. In another study, APPs, plasma and urinary TNF, interleukin-6, interleukin-8 and adhesive molecules ICAM-1, VCAM-1 were found to be significantly different in various glomerulopathies. Finally, our experimental data indicate the nitric oxide participation in oestradiol regulation of coeruloplasmin synthesis in rat.
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PMID:[Acute phase proteins]. 871 1


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