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

Neural crest-derived cells populate the thymus, and their coexistence with epithelial cells is required for proper organ development and T cell education function. We show here that epidermal growth factor (EGF), a major epithelial cell growth-enhancing agent, has a morphogenetic action to promote the expression of a neuronal phenotype (e.g., neurofilament expression) in cultured thymic epithelial cells that are characterized by a cytokeratin-positive epithelial cell background. The proliferation of such neurodifferentiated cells is also enhanced by EGF. Furthermore, the growth factor enhances cells that express the genes encoding the preprotachykinin A-generated neuropeptides and bipotential neuropoietic and lymphopoietic cytokines ciliary neurotrophic factor and interleukin-6. These cytokines also enhance the neuronal phenotype of thymic epithelial cells. Therefore, EGF appears to be a composite autocrine/paracrine neuromodulator in thymic stroma. This suggests that EGF may regulate thymus-dependent immune functions by promoting neuronal gene expression in neural crest-derived cells.
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PMID:Epidermal growth factor promotes a neural phenotype in thymic epithelial cells and enhances neuropoietic cytokine expression. 754 Jun 16

Supraphysiological levels of glucocorticoids, whether endogenous (Cushing's syndrome) or exogenous (glucocorticoid therapy), inhibit growth in children and immature animals. This effect has long been suspected to be due to glucocorticoid antagonism of GH action at the level of peripheral tissues. In the present study we demonstrate direct antagonism of GH action at the cellular level by the artificial glucocorticoid dexamethasone. Dexamethasone was found to inhibit the ability of GH to elicit several early events in GH signaling in 3T3-F442A fibroblasts. Dexamethasone (100 nM) for 24 h decreases by 50-75% GH-induced tyrosyl phosphorylation of mitogen-activated protein kinases ERK1 and ERK2, the transcription factor Stat3/APRF, the GH receptor-associated tyrosine kinase JAK2, and the GH receptor. These effects appear to be specific to GH. Dexamethasone does not inhibit induction of tyrosyl phosphorylation of ERK proteins by epidermal growth factor or phorbol myristate acetate, nor does it block induction of tyrosyl phosphorylation of Stat3/APRF by leukemia inhibitory factor or interleukin-6, or induction of JAK2 by leukemia inhibitory factor or interferon-gamma. Dexamethasone does not decrease the expression of ERK1 or -2, Stat3, or JAK2 proteins. Rather, the effects of dexamethasone on GH action appear to be due to a decrease in the number of GH receptors in the plasma membrane. Twenty-four-hour treatment with dexamethasone leads to a 50% decrease i GH binding, which Scatchard analysis suggests is due to a decrease in GH receptor number. These findings suggest that glucocorticoids antagonize cellular GH action by decreasing GH binding, suggesting a mechanism by which systemic glucocorticoids could antagonize GH action in peripheral tissues.
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PMID:Dexamethasone-induced antagonism of growth hormone (GH) action by down-regulation of GH binding in 3T3-F442A fibroblasts. 758 9

The bone marrow microenvironment consists of stromal cells and extracellular matrix components which act in concert to regulate the growth and differentiation of hematopoietic stem cells. There is little understanding of the mechanisms which modulate the regulatory role of stromal cells. This study examined the hypothesis that mesenchymal growth factors such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) modulate stromal cell activities and thereby influence the course of hematopoiesis. Both bFGF and EGF were potent mitogens for marrow stroma. However, both factors proved to be inhibitory to hematopoiesis in primary long-term marrow cultures. Inhibition was also observed when hematopoietic cells and bFGF or EGF were added to subconfluent irradiated stromal layers, demonstrating that the decline of hematopoiesis was not due to overgrowth of the stromal layer. Loss of hematopoietic support in bFGF and EGF was dose-dependent. Removal of bFGF and EGF permitted stromal layers to regain their normal capacity to support hematopoiesis. In stroma-free long-term cultures, neither factor affected CFU-GM expansion. Basic FGF slightly enhanced granulocyte-macrophage colony forming unit (CFU-GM) cloning efficiency in short-term agarose culture. Basic FGF did not reduce the levels of interleukin-6 (IL-6), GM-CSF, or G-CSF released by steady state or IL-1-stimulated stroma. Similarly, the constitutive levels of steel factor (SF) mRNA and protein were not affected by bFGF. Basic FGF did not alter the level of TGF-beta 1 in stromal cultures. We conclude that bFGF and EGF can act as indirect negative modulators of hematopoietic growth in stromal cultures. The actual mediators of regulation, whether bound or soluble, remain to be identified.
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PMID:Basic fibroblast growth factor and epidermal growth factor downmodulate the growth of hematopoietic cells in long-term stromal cultures. 759 17

The gene expression of five matrix metalloproteinases (MMPs) and two tissue inhibitors of metalloproteinases (TIMPs) was studied in human gliomas in vivo and in vitro to evaluate their roles in glioma invasion. Simultaneous expression of one to four MMP genes and two TIMP genes was found in 17 surgical glioma specimens, and one MMP (gelatinase A) gene and two TIMP genes were simultaneously expressed in tissue of three brains. The concomitant overexpression of gelatinase A, gelatinase B, and occasional matrilysin genes was associated with the malignancy of gliomas and accompanied by overexpression of the TIMP-1 gene. In five human glioma cell lines, gelatinase A, TIMP-1, and TIMP-2 genes were constitutively expressed in alll cell lines: the matrilysin gene in three cell lines; the stromelysin gene in two cell lines; and the interstitial collagenase gene in one cell line. There was a clear difference in the expression of gelatinase B and stromelysin genes between surgical glioma specimens and glioma cell lines: the gelatinase B gene was not expressed constitutively in vitro but was overexpressed in vivo, whereas the stromelysin gene was not expressed in vivo but was expressed in some cell lines. To find the cause of that difference in vivo and in vitro, the transcriptional regulations of MMP and TIMP genes by tumor promoter, growth factors, or cytokines were studied in vitro. Interstitial collagenase, gelatinase B, stromelysin, and TIMP-1 genes were upregulated in many cell lines by phorbol-12-myristate-13-acetate (PMA) and in some cell lines by epidermal growth factor, tumor necrosis factor-alpha, or interleukin-1 beta. Transforming growth factor-beta 1 (TGF beta 1) upregulated gelatinase A and matrilysin genes in some cell lines, and there were no clear responses from any MMP and TIMP genes to interleukin-6. Thus, the transcriptional modulation of MMP genes by these growth factors and cytokines seemed insufficient to explain the difference in gelatinase B and stromelysin gene expressions in vivo and in vitro and was suggestive of the genetic alteration of glioma cells in vitro, the heterogeneous cell population in glioma tissues, or both. Furthermore, the in vitro invasion of glioma cells through Matrigel in response to PMA, TGF beta 1, or TIMP-1 was assessed by chemoinvasion assay. In most cell lines, invasion was significantly stimulated by PMA or TGF beta 1 but suppressed by TIMP-1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gliomas. 761 76

Liver regeneration in response to partial hepatectomy is a physiological growth response observed in the intact animal. Understanding the early signals that trigger liver regeneration is of vital importance to understand the liver's response to injury. It has been observed that several growth factors and cytokines, including epidermal growth factor (EGF) and interleukin-6 (IL-6), can activate members of the signal transducers and activators of transcription (Stat) family of transcription factors resulting in tyrosine phosphorylation of these factors, nuclear translocation, and an active DNA binding transcriptional complex. Because Stat3 participates in the regulation of primary growth response genes, we wondered if it is induced in the early phase of liver regeneration. We found that Stat3 DNA-binding activity is increased in the remnant liver within 30 minutes of partial hepatectomy and peaks at more than 30-fold at 3 hours. This induction is not observed after sham surgery. The induction of Stat3 appears to be part of the initial response of the remnant liver to partial hepatectomy, because it occurs in the presence of cycloheximide-mediated protein synthesis blockade. Activation of Stat3 is unusual, because it extends beyond the immediate-early time period and remains near peak level at 5 hours posthepatectomy. Although insulin-treated H35 cells activate many of the same immediate-early genes as regenerating liver, Stat3 is not induced in these cells. Because Stat factors are known to be inactivated by protein tyrosine phosphatases (PTPase), we showed that a PTPase is able to eliminate the DNA binding of hepatic Stat3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid activation of the Stat3 transcription complex in liver regeneration. 773 51

The present study was performed on primary cultures of mouse astrocytes and cultures of rat pheochromocytoma PC-12 in order to investigate the regulation of the prion protein (PrP) gene expression in relation to proliferation and differentiation. Treatment of PC-12 cells with interleukin-6 (IL-6) and beta-nerve growth factor (NGF) resulted in induction of neuronal differentiation. Northern blot analysis demonstrated a 4-fold increase of PrP mRNA in relation to cellular differentiation, after 7 days of treatment with either of the two factors. In astrocytes, PrP and glial fibrillary acidic protein (GFAP) mRNA levels were found to be regulated in a similar manner during development in vitro. A 3-fold increase of their mRNAs was observed from 5 to 14 days of culture (proliferation period). Then, their gene expressions showed a slight decrease from 14 to 28 days (maturation period). Treatment of astrocytes with IL-6, basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) appeared to markedly down-regulate the expression of GFAP mRNAs, which might reflect cell maturation. In contrast, they had no significant effect on the expression of PrP gene. These results suggest that the PrP gene expression is differently regulated in neural cells. In neuronal cells, it is mainly associated with differentiation. On the other hand, in astrocytes, the PrP mRNA level seems to be not only related to the proliferation and differentiation stages.
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PMID:Modulation of prion protein gene expression by growth factors in cultured mouse astrocytes and PC-12 cells. 791 3

Mammary gland factor (MGF) is a transcription factor discovered initially in the mammary epithelial cells of lactating animals. It confers the lactogenic hormone response to the milk protein genes. We reported recently the isolation of the cDNA encoding MGF. MGF is a novel member of the cytokine-regulated transcription factor gene family. Members of this gene family mediate interferon alpha/beta and interferon gamma induction of gene transcription, as well as the response to epidermal growth factor and interleukin-6, and have been named signal transducers and activators of transcription (Stat). The name Stat5 has been assigned to MGF. We studied the mechanisms involved in the prolactin activation of Stat5 in COS cells co-transfected with cDNA encoding Stat5 and the prolactin receptor. Prolactin treatment of the transfected cells caused activation of Stat5 within 5-10 min. This activation does not require ongoing protein synthesis. Tyrosine kinase inhibitors prevent Stat5 activation in transfected COS cells. Treatment of recombinant Stat5 with a tyrosine-specific protein phosphatase in vitro abolishes its DNA binding activity. Prolactin stimulation of transfected cells induces Stat5 phosphorylation on tyrosine. Phosphorylation of in vitro transcribed and translated Stat5 with the Jak2 tyrosine kinase, but not with fyn, lyn or lck, confers DNA binding activity. The prolactin response of the beta-casein milk protein gene promoter can be observed in COS cells transfected with cDNA vectors encoding Stat5 and the long form of the prolactin receptor. The short form of the prolactin receptor is unable to promote Stat5 phosphorylation and confer transcriptional induction in COS cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. 792 80

The placental members of the prolactin-GH-placental lactogen (PL) gene family of the mouse include mPL-I, mPL-II, proliferin (PLF) and proliferin-related protein (PRP). The aim of the present study was to assess the effects of tumour necrosis factor-alpha (TNF-alpha) on the secretion of these proteins in primary cultures of placental cells from days 7, 9 and 12 of pregnancy. The effects of epidermal growth factor (EGF) on the secretion of PLF and PRP were also determined. EGF has previously been shown to stimulate mPL-I and inhibit mPL-II secretion. Incubation of placental cells from day 7 of pregnancy for 5 days with 10 nmol human (h)TNF-alpha/l did not affect the mPL-II concentration of the medium, but similar treatment of cells from days 9 or 12 of pregnancy resulted in a significant reduction in the mPL-II concentration of the medium by the second or third day of culture. The intracellular concentration of mPL-II, the number of cells that released mPL-II as assessed by reverse haemolytic plaque assay, and steady-state levels of mPL-II mRNA as assessed by Northern analysis were also reduced by hTNF-alpha treatment. The lowest concentration of hTNF-alpha that significantly inhibited mPL-II secretion by cells from day 12 of pregnancy was 0.01 nmol/l. hTNF-alpha treatment did not affect the secretion of mPL-I, PLF or PRP, as assessed by the concentrations of these proteins in the medium during a 5-day incubation. Incubation of the cells with 20 ng EGF/ml also did not affect the PLF or PRP concentration of the medium during 5 days of culture. To determine whether the effect of hTNF-alpha on mPL-II secretion was mediated by interleukin-6 (IL-6), the IL-6 concentration of the medium of control and hTNF-alpha-treated cells was determined. Bioactive and immunoreactive IL-6 could not be detected in medium from either treatment group. The presence of binding sites for hTNF-alpha was assessed in cells from day 12 of pregnancy. Scatchard analysis detected a single class of binding sites having a Kd of 1.61 +/- 0.34 nmol/l, with about 1350 sites per cell. The results of this study demonstrate that hTNF-alpha inhibits the secretion of mPL-II by placental cells from days 9 and 12 of pregnancy, suggesting that TNF-alpha may be one of the factors that regulate the production of this hormone in vivo.
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PMID:Selective inhibition of mouse placental lactogen II secretion by tumour necrosis factor-alpha. 796 26

The expression and function of gonadotropin receptors, and the secretion of steroids, transferrin, and cytokines were investigated in three immortalized (single transfection with v-myc) mouse granulosa cell lines (GRM01, GRM01L, and GRM02). A dose-dependent increase in progesterone production was obtained in GRM01 and GRM02 cells after addition of LH, FSH, modulators of the adenylate cyclase enzyme system, and cAMP analogues. The LH-induced release of progesterone was already detectable in GRM02 cells after 8 h and was related to incubation time and cell number. Both epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) induced the secretion of progesterone in GRM02 cells, while no effect was obtained with TGF beta. LH receptor concentration was highest in the GRM02 cell line. FSH receptor mRNA was visualized in GRM01 and GRM02 cells. Aromatase activity in GRM02 cells was induced by androgens and inhibited by aromatase inhibitors. Whereas all cell lines were able to secrete transferrin, only in GRM01 cells was transferrin secretion increased significantly by LH. FSH did not affect transferrin secretion in the three cell lines, in contrast to forskolin or 8-bromo-cAMP. The immortalized mouse granulosa cell lines were able to express and release several growth factors. The expression and secretion of activin, inhibin, TGF beta, EGF, TGF alpha, insulin-like growth factor II, fibroblast growth factor (acidic and basic), platelet-derived growth factor, and interleukin-6 suggest an autocrine or paracrine role for these factors in follicular differentiation and function. In conclusion, these cells, derived from mural granulosa cells and immortalized in a preovulatory state, can be used to study granulosa cell physiology or to study the role of granulosa cells and their derivatives in the process of follicular maturation, fertilization, and early embryonic development.
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PMID:Secretion of steroids, growth factors, and cytokines by immortalized mouse granulosa cell lines. 802 76

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


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