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

Interleukin-6 (IL-6) is a potent stimulator of bone resorption which has been demonstrated in a variety of in vivo and in vitro models. We investigated the regulation of IL-6 secretion in primary human osteoblastic cells (HOC) in vitro by cytokines known to play an important role in coupling bone formation to bone resorption. HOC were isolated from healthy adults who underwent selective orthopedic surgery and treated with cytokines released in the bone microenvironment during coupling i.e Interleukin-1beta (IL-1beta), Tumor Necrosis Factor alpha (TNFalpha), Transforming Growth Factor beta1 and 2 (TGFbeta 1 and 2) and Endothelin-1 (ET-1). Furthermore, we determined whether systemically-acting steroid hormones of gonadal and adrenal origin as well as glucocorticoids affect the local regulation of IL-6 secretion in primary HOC. To examine the effects of different steroid hormones on IL-6 production, HOC were exposed to estradiol (E2), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and dexamethasone (Dexa) with and without a subsequent treatment of the HOC populations with cytokines. We observed that (1) IL-1beta and TNFalpha induced IL-6 in a dose and time-dependent fashion, (2) TGFbeta 1 and 2 enhanced basal and IL-1beta and TNFalpha induced IL-6 expression, (3) ET-1 elicited a dose-dependent stimulatory effect on IL-6 expression. (4) E2, DHT and DHEA alone and in combination with IL-1beta and TNFalpha elicited no reproducible dose-dependent effect on IL-6 production, whereas Dexa inhibited basal and IL-1beta and TNFalpha induced IL-6 expression dose dependently. In conclusion, IL-1beta, TNFalpha, TGFbeta 1 and 2 and ET-1 may participate in the regulation of bone resorption by stimulating IL-6 expression in HOC. Dexa inhibits the constitutive and cytokine stimulated IL-6 expression, whereas there is no in vitro evidence that sex steroids exert a major inhibitory effect on the osteoblastic secretion of IL-6 as demonstrated in a primary human bone cell model.
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PMID:Regulation of interleukin-6 expression in human osteoblastic cells in vitro. 979 66

We investigated putative roles of transforming growth factor (TGF)-beta expressed in peripheral ganglia in the regulation of neuronal cell survival during the period of ontogenetic neuron death (OD). The chick ciliary ganglion (CG), where OD occurs between embryonic days (E) 6 and 10, was employed as a model system. We show that CG neurons (E8) are immunoreactive (ir) for TGF-beta2 and -beta3 as well as the TGF-beta receptor TbetaR-II, but are not ir for TGF-beta1. Ciliary neurotrophic factor (CNTF) and fibroblast growth factor (FGF)-2, established neurotrophic molecules for CG neurons, up-regulate TGF-beta3 mRNA and TGF-beta biological activity in cultures of E8 CG neurons. None of the TGF-beta isoforms--beta1, beta2, or beta3--has a trophic, survival-promoting effect on cultured CG neurons. However, all isoforms enhance CG neuron survival mediated by CNTF or FGF-2, significantly and over a wide range of concentrations. In combination with the neurotrophins (NT) nerve growth factor (NGF) and NT-3, which are not neurotrophic for CG neurons, TGF-beta significantly promotes CG neuron survival. However, TGF-beta does not act synergistically with the neuropoietic cytokines oncostatin M, leukemia inhibiting factor, or interleukin-6. Immunoneutralization of endogenous TGF-beta released from CG neurons using an antibody to TGF-beta1/-beta2/-beta3 significantly reduces the potency of CNTF or FGF-2 to promote CG neuron survival. The blocking effect of the anti-pan-TGF-beta antibody could be rescued by adding exogenous TGF-beta. Together, these data suggest that para-/autocrine TGF-beta signaling has an important effect on the regulation of neuron survival in a model system of peripheral neurons.
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PMID:TGF-beta regulates the survival of ciliary ganglionic neurons synergistically with ciliary neurotrophic factor and neurotrophins. 985 58

Transforming growth factor-beta has complex activities on hematopoietic cells. We have previously shown that murine long-term repopulating activity is compromised by ex vivo culture in TGF-beta 1 and conversely is increased by abrogating endogenous TGF-beta activity with a neutralizing antibody. In the current study, we investigated the effect of abrogation of autocrine or paracrine TGF-beta present during retroviral transduction on gene transfer efficiency to primitive hematopoietic cells. Murine marrow cells were cultured and retrovirally transduced for 4 days in the presence of interleukin-3, interleukin-6 and stem cell factor, and either a neutralizing anti-TGF-beta antibody or an isotype control. Committed progenitor cells were analyzed for gene transfer efficiency, and cells were also injected into W/Wv recipient mice for analysis of transduction of long-term repopulating cells. The progenitor (CFU-C) transduction efficiency in the presence of anti-TGF-beta was significantly greater. Semiquantitative PCR analysis and Southern blot analysis for the retroviral marker gene in the blood and bone marrow of recipient mice revealed a significant increase in the transduction efficiency of long-term repopulating cells after culture and transduction in the presence of the anti-TGF-beta. Thus neutralization of TGF-beta activity during retroviral transduction allows more efficient gene transfer into primitive murine hematopoietic cells and may prove beneficial in future clinical gene transfer or therapy trials.
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PMID:Abrogation of TGF-beta activity during retroviral transduction improves murine hematopoietic progenitor and repopulating cell gene transfer efficiency. 993 Mar 29

In this study, we examined the role of fibrogenic cytokines in alcohol-induced fibrosis. In particular, we examined the production of a novel fibrogenic cytokine, fibrosin, among others, by fibroblasts in response to ethanol in vitro; we also studied the production of fibrosin in an animal model of alcohol-induced liver injury. This model system utilizes the intragastric feeding rat model in which rats are fed different dietary fats and ethanol or dextrose. Our study showed that physiologic concentrations of ethanol directly induced proliferation of fibroblasts in vitro and also stimulated the production of cytokines. In particular, fibrosin, the novel fibrogenic cytokine, was produced. Other cytokines such as TGFbeta, IL-6, and TNFalpha were also induced. Also, exposure of fibroblasts to interleukin-1beta, interleukin-6, and tumor necrosis factor alpha induced production of fibrosin. In the fish oil-ethanol-fed rats which showed fibrotic lesions in the liver, fibrosin mRNA as well as protein was expressed. Fibrosin was not detected in control rats not exhibiting fibrosis. These studies show that ethanol can directly stimulate fibroblast proliferation and production of fibrogenic cytokines. It is likely that fibrosin, which may be derived from inflammatory cells, contributes to alcohol-induced hepatic fibrosis in vivo.
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PMID:Fibrosin: A novel lymphokine in alcohol-induced fibrosis. 1049 91

The objective of this study was to assess the influence of specific factors on post-thaw development of mouse cryopreserved morulae. Thawed morulae (n = 206) were randomly distributed between 10 treatment groups: medium alone control (CT), Vero (VR) cells, leukaemia inhibitory factor (1 ng/ml), interleukin-6 (1 ng/ml), transforming growth factor (TGF) alpha (2 ng/ml), epidermal growth factor (EGF) (4 ng/ml), platelet-derived growth factor (1 ng/ml), insulin-like growth factor (IGF)-I (30 ng/ml), IGF-II (1 ng/ml) and TGFbeta (2 ng/ml). At 4, 8, 20, 30 and 48 h, a digitized image of each thawed embryo was captured and stored for later analysis. The following parameters were examined: blastocoel formation, blastocyst expansion, zona thickness and hatching. At termination of the experiment, cell number per embryo was determined by bisbenzimide staining. When contrasted to the medium alone control, co-culture consistently accelerated the development of frozen-thawed morulae to the hatched blastocyst stage, allowing embryos to recover rapidly from any damage sustained during the cryopreservation process. While no single growth factor/cytokine was able to completely mimic the results achieved with co-culture, all of the growth factors impacted positively on at least one of the morphological parameters studied. Cell proliferation was significantly stimulated by just 48 h exposure to growth factors, either through co-culture or by direct media supplementation. Co-culture again yielded the best results with a mean cell count of 217 +/- 76 cells per blastocyst as compared with 131 +/- 36 in control medium alone. Amongst the factors tested, IGF-I, IGF-II and EGF had the greatest impact, with mean cell counts of 172 +/- 50, 168 +/- 50 and 179 +/- 55 respectively. Whereas only 5% of CT embryos developed to blastocysts with > 200 cells, 51% of thawed embryos placed on co-culture monolayers and 25-32% of embryos cultured with IGF-I, IGF-II or EGF had > 200 cells. This study for the first time systematically describes the effect of culture regimen and growth factor additives on the post-thaw development of cryopreserved embryos.
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PMID:Assessment of growth factor effects on post-thaw development of cryopreserved mouse morulae to the blastocyst stage. 1065 14

Using reverse transcription polymerase chain reaction (RT-PCR), we have studied the temporal expression of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), transforming growth factor-beta 1 (TGF-beta 1), and tumor necrosis factor-alpha (TNF-alpha) mRNAs in three axotomy paradigms with distinct functional outcomes. Axotomy of adult rat facial motoneurons results in neuronal regeneration, axotomy of neonatal facial motoneurons results in neuronal apoptosis, and axotomy of rubrospinal neurons results in neuronal atrophy. Our RT-PCR findings show that a significant and sustained upregulation of IL-6 mRNA is associated uniquely with the regeneration of adult facial motoneurons. Histochemical studies using IL-6 immunohistochemistry show intense IL-6 immunoreactivity in axotomized adult facial motoneurons. Assessment of reactive glial changes with astroglial and microglial markers reveals that the reactive gliosis following adult facial nerve axotomy is more intense than that observed in either of the other two paradigms. Exposure of cultured microglial cells to IL-6 stimulates microglial proliferation in a dose-dependent manner. Cultured microglia also show expression of IL-6 receptor mRNA, as determined by RT-PCR. Our findings support the idea that reactive gliosis is required for neuron regeneration to occur, and more specifically, they suggest that neuron-derived IL-6 serves as a signalling molecule that induces microglial proliferation during motoneuron regeneration.
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PMID:Comparative evaluation of cytokine profiles and reactive gliosis supports a critical role for interleukin-6 in neuron-glia signaling during regeneration. 1086 95

Although it is generally accepted that destruction and remodeling of temporal bone associated with middle ear cholesteatoma is mainly caused by the action of osteoclasts, it has been shown that neutral collagenases also play a role in predigesting the osteoid layer and exposing the mineralized bone to osteoclastic activity. Here we show that gelatinase B (matrix metalloproteinase-9) is over-expressed in cholesteatoma compared to external ear canal skin (EACS). Expression of MMP-9 in cholesteatoma mainly occurs in suprabasal layers, and more rarely in basal layers of cholesteatoma epithelium, as well as in inflammatory cells of the perimatrix. We further analyzed the influence of cholesteatoma debris, cholesteatoma granulation tissue, and cholesteatoma components such as keratin, cholesterol and bacterial endotoxin on the expression of MMPs in EACS keratinocytes. We show that cholesteatoma debris and granulation tissue extract both induced the secretion of MMP-9 by EACS keratinocytes, while keratin. bacterial lipopolysaccharide (LPS) or cholesterol did not show any effect. We further performed co-incubation and immunoprecipitation experiments using neutralizing interleukin-1alpha, EGF, TGF-beta, TGF-alpha, interleukin-6 and TNF-alpha antibodies. Inhibition of MMP-9 up-regulation by debris or granulation tissue extract could be revealed with diverse cytokine antibodies. The results are discussed with regard to previously published studies.
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PMID:Induction of matrix metalloproteinases in keratinocytes by cholesteatoma debris and granulation tissue extracts. 1107 91

Serum levels of inflammatory cytokines and chemokines were measured in 132 patients with chronic idiopathic neutropenia of adults (CINA) and 34 healthy volunteers (controls) using commercially available micro-ELISA determination kits. We found that serum interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), transforming growth factor-beta(1) (TGF-beta(1)), and soluble tumor necrosis factor receptor p55 (sTNF-RI) were all significantly increased in CINA patients compared to controls. Individual cytokine values inversely correlated with the number of circulating neutrophils. Serum levels of interleukin-8 (IL-8) and RANTES, two potent chemokines for neutrophils and lymphocytes, respectively, were also significantly increased in the group of patients and they inversely correlated with the number of circulating neutrophils. Contrarily, serum levels of interleukin-4 (IL-4), interferon-gamma (IFN-gamma), soluble CD23 (sCD23), and soluble interleukin-2 receptor (sIL-2R) did not show any significant change in the patients studied. We assume that CINA patients have increased serum concentrations of inflammatory cytokines and chemokines mainly produced by activated macrophages, while they disclose normal levels of inflammatory molecules mainly released from activated lymphocytes. These findings provide further evidence for an underlying low-grade chronic inflammatory process in CINA patients, as we previously have suggested. If this chronic inflammation is really the cause of the disorder or it simply represents the result of neutropenia remains to be elucidated.
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PMID:Patients with chronic idiopathic neutropenia of adults have increased serum concentrations of inflammatory cytokines and chemokines. 1107 51

Interleukin-6 (IL-6) is a pleitrophic cytokine that not only regulates growth and differentiation of many cell types, but also induces production of acute phase proteins (AAP) in hepatocytes. Our previous works have demonstrated that both PI 3-K/Akt and STAT3 pathways were concomitantly activated and cooperatively mediated the anti-apoptotic effect of IL-6. This investigation reports that IL-6 protected cells against apoptosis induced by a variety of agents including, TGF-beta, UV and retinoic acid (RA) in Hep3B cells, suggesting that IL-6 is a fundamental determinant of hepatic cell survival. Mcl-1, but not other Bcl-2 family members, was rapidly up-regulated by IL-6, with a peak (approximately 3-4-fold) appearing at 4 h. Transient transfection of cells with a mcl-1 antisense vector, resulting in a 50-60% reduction of the anti-apoptotic effect of IL-6, indicating that Mcl-1 is a downstream effector of IL-6. Which signaling pathway transduced by IL-6 responsible for the Mcl-1 up-regulation was further investigated. In Hep3B cells, the JAK/STAT3, ERK, and PI 3-K/Akt pathways were activated by IL-6 stimulation. Blocking JAK/STAT3 activation with a dominant-negative mutant STAT3F or a JAK inhibitor AG490 could not influence IL-6-mediated Mcl-1 up-regulation. Similarly, PD98059 treatment, a MEK specific inhibitor, also failed to inhibit Mcl-1 expression. However, the IL-6-induced Mcl-1 up-regulation was effectively attenuated in the presence of PI 3-K inhibitors, LY294002 and wortmannin. Expression of dominant-negative Akt, but not Etk, could abrogate the IL-6-induced increase of Mcl-1. In conclusion, our results suggest that the anti-apoptotic effect of IL-6 is mediated, at least in part, by Mcl-1 expression and that is mainly through the PI 3-K/ Akt-dependent pathway.
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PMID:The involvement of PI 3-K/Akt-dependent up-regulation of Mcl-1 in the prevention of apoptosis of Hep3B cells by interleukin-6. 1131 1

Pituitary folliculostellate (FS) cells are usually located between the secretory cells in the anterior pituitary, and they produce many peptides that exert a paracrine effect on hormone-producing pituitary cells. Previous approaches have been unsuccessful in obtaining homogeneous populations of FS cells. We used a combination of immunostaining with S100 protein followed by laser capture microdissection (Immuno-LCM) to obtain purified populations of rat FS cells. These cells were analyzed along with a mouse FS cell line (TtT/GF) by RT-PCR for gene expression. RT-PCR analyses showed that both FS cell populations expressed the mRNAs for glial fibrillary acidic protein, S100 protein, transforming growth factor-beta1 (TGFbeta1), TGFbeta receptor, interleukin-6, leptin, leptin receptor, pituitary adenylate cyclase-activating polypeptide (PACAP), and PACAP receptors. Both FS cell populations were negative for PRL, GH, and POMC, supporting the homogeneity of the rat FS cell population. TGFbeta1, but not PACAP-38, treatment stimulated cell proliferation in both FS cell populations. TGFbeta1 increased leptin, but not interleukin-6, mRNA expression in rat FS cells. However, TGFbeta1 inhibited leptin RNA expression in the TtT/GF cell line, as shown by RT-PCR and Northern blot analysis. These results indicate that 1) homogeneous populations of FS cells can be prepared by Immuno-LCM; 2) TGFbeta1 stimulates the proliferation of normal rat FS cells and the TtT/GF cell line; and 3) the effects of TGFbeta1 to stimulate leptin mRNA expression in rat FS cells but inhibit leptin mRNA expression in TtT/GF cells probably reflect alterations in signal transduction in the TtT/GF cell line.
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PMID:Analysis of homogeneous populations of anterior pituitary folliculostellate cells by laser capture microdissection and reverse transcription-polymerase chain reaction. 1131 32


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