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)

Cytokines constitute a major class of mediators responsible for "activation" of hepatic stellate cells (HSCs) in vitro and in vivo. They are largely divided into mitogenic (transforming growth factor-alpha, platelet-derived growth factor, interleukin-1, tumor necrosis factor-alpha, and insulin-like growth factor) and fibrogenic (transforming growth factor-beta and interleukin-6) cytokines. In addition to their mitogenic (stimulation of cell proliferation) and fibrogenic (induction of matrix proteins) properties, they are also shown to confer in vitro unique cellular changes known to be the key features of HSC "activation," including loss of vitamin A, stimulation of migration, enhanced cellular contractility, and matrix metalloproteinase and tissue inhibitor of metalloproteinase induction. Potential cellular sources of the cytokines consist of hepatic macrophages, endothelial cells, biliary epithelial cells, lymphocytes, platelets, hepatocytes, and activated HSCs. To better understand the mode of actions and the pathogenetic significance of cytokines/chemokines involved in "activation" of HSCs, the following four questions need to be addressed: (1) What other cytokines are expressed by HSCs to establish critical autocrine stimulation? (2) What are endogenous or exogenous priming factors for HSC stimulation? (3) What is the mechanism of activation for transforming growth factor-beta, the pivotal fibrogenic cytokine? (4) How important are HSC-derived proinflammatory mediators in liver fibrosis? This review will discuss these questions, along with the current understanding of the role of cytokines in HSC activation.
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PMID:Cytokine regulation of hepatic stellate cells in liver fibrosis. 1037 13

Altered function of the fibroblasts is thought to contribute to the pathogenesis of psoriasis. To further elucidate this point, we compared the ability of fibroblasts from psoriatic lesions and of fibroblasts from healthy individuals to produce interleukin-6 (IL-6). The IL-6 levels were measured by ELISA in serum-free culture medium before and after stimulation of monolayer fibroblasts with various concentrations of tumour necrosis factor-alpha (TNF-alpha), platelet-derived growth factor (PDGF), and interferon-gamma (IFN-gamma), alone and in different combinations. The production of IL-6 in the fibroblast cultures was stimulated by TNF-alpha (0.01-10 nm/ml medium) in a dose-dependent way. Fibroblasts from psoriatic lesions produced lower amounts of IL-6 than fibroblasts from healthy individuals both before and after stimulation with the different concentrations of TNF-alpha (P = 0.012). The ratios between the IL-6 concentrations before and after stimulation with TNF-alpha were similar in both types of fibroblasts, indicating that the capacity to produce IL-6 is reduced in psoriatic fibroblasts compared with healthy ones. The production of IL-6 was not influenced by either PDGF or IFN-gamma. These findings support the view that the phenotype of the fibroblast is altered in psoriasis.
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PMID:Psoriatic fibroblasts secrete lower amounts of IL-6 than healthy fibroblasts before and after stimulation with TNF-alpha. 1055 11

We report the unusual occurrence of Kaposi's sarcoma following asbestos-related malignant mesothelioma, in a human deficiency virus (HIV)-negative Italian man. Seropositivity to human herpes virus 8 (HHV8) was documented at the time of mesothelioma diagnosis and preceded the onset of Kaposi' sarcoma with a time lapse of 13 months. HHV8 DNA was detected by polymerase chain reaction in lesional Kaposi's sarcoma but not within mesothelioma. By immunostaining, mesothelioma cells expressed interleukin-6 and platelet-derived growth factor, which are important for survival of Kaposi's sarcoma cells. Besides the possibility of a casual association, we hypothesize that mesothelioma-linked factors may have contributed to the development of Kaposi's sarcoma in the presence of HHV8 infection.
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PMID:Kaposi's sarcoma following malignant mesothelioma. 1062 4

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

In order to evaluate whether or not polyethylene terephthalate coated with pyrolytic carbon and collagen (PET+PC) favors inflammatory or hyperplastic reactions, the expression of mRNAs specific for interleukin-6 (IL-6), platelet-derived growth factor-A (PDGF-A), PDGF-B, transforming growth factor-beta1 (TGF-beta1), and TGF-beta2 were tested in vitro by cultured human umbilical vein endothelial cells (HUVEC). The cultures were put in contact with PET+PC for 1, 24, 48, and 72 h. The same cells cultured on polystyrene without biomaterials were tested as negative controls; cultures incubated with LPS were the positive control. The expression of mRNAs was evaluated by RT-PCR with specific primers. PET+PC did not determine any differences in the expression of IL-6-specific mRNA at any of the incubation times compared to the negative control while LPS (the positive control) induced expression after 24, 48, and 72 h. PET+PC induced a more precocious expression of mRNA specific for PDGF-A than did the negative control; however, the expression no longer was present after 48 h while in the negative control the expression stopped after 72 h. PET+PC induced a less frequent expression of PDGF-B-specific mRNA than did the negative control and LPS, especially after 24 h. PET+PC induced a later expression of TGF-beta2-specific mRNA than did the negative control and a less frequent expression of mRNA specific for TGF-beta1 after 24 and 72 h.
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PMID:Cytokine expression in vitro by cultured human endothelial cells in contact with polyethylene terephthalate coated with pyrolytic carbon and collagen. 1075 6

Members of the STAT family of transcriptional regulators modulate the expression of a variety of gene products that promote cell proliferation, survival and transformation. Although initially identified as mediators of cytokine signaling, the STAT proteins are also activated by, and thus may contribute to the actions of, polypeptide growth factors. To define the mechanism by which these factors activate STATs, we examined the process of Stat3 activation in Balb/c-3T3 fibroblasts treated with platelet-derived growth factor (PDGF). As STATs are activated by tyrosine phosphorylation, and as PDGF receptors are ligand-activated tyrosine kinases, we considered the possibility that Stat3 interacts with and is phosphorylated by PDGF receptors. We find that Stat3 associates with PDGF beta receptors in both the presence and, surprisingly, the absence of PDGF. Moreover, Stat3 was phosphorylated on tyrosine in PDGF beta receptor immunoprecipitates of PDGF-treated but not untreated cells. Although required, receptor activation was insufficient for Stat3 activation. When added to cells in combination with a pharmacologic agent (PD180970) that specifically inhibits the activity of Src family tyrosine kinases, PDGF did not activate Stat3 as monitored by electrophoretic mobility shift assay. PD180970 did not affect MAPK activation by PDGF or the JAK-dependent activation of Stat3 by interleukin-6. The necessity of Src activity for Stat3 activation by PDGF was further evidenced by data showing the presence of Src in complexes containing both Stat3 and PDGF beta receptors in PDGF-treated cells. These results suggest a novel mechanism of STAT activation in which inactive Stat3 pre-assembles with inactive PDGF receptors, and in response to ligand binding and in a manner dependent on Src kinase activity, is rapidly phosphorylated and activated. Additional data demonstrate that Src kinase activity is also required for PDGF stimulation of DNA synthesis in density-arrested cells.
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PMID:Activation of Stat3 preassembled with platelet-derived growth factor beta receptors requires Src kinase activity. 1081 99

Activator protein-1 (AP-1) plays an important role in the regulation of gene expression in mesangial cells (MC) during the pathogenesis of glomerular inflammatory disease. The precise regulation of the AP-1 family by agents that are known to activate MC is, however, poorly understood. The action of platelet-derived growth factor (PDGF) and, for the first time, lipopolysaccharide (LPS), interleukin-6 (IL-6), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on AP-1 gene expression in MC was therefore studied. Whilst the expression of JunD was not affected by any of the mediators, the mRNA levels of c-fos and JunB were induced by LPS, IL-6, IFN-gamma, PDGF and TNF-alpha, and that of c-jun by LPS, IFN-gamma, PDGF and TNF-alpha. Electrophoretic mobility shift assays showed a time-dependent increase in AP-1 DNA binding activity with JunB representing the major mediator-inducible member involved in DNA-protein interactions. However, stimulus-specific changes in the kinetics and magnitude of AP-1 mRNA expression and DNA binding activity were identified and, additionally, the results showed the potential existence of cell-type-specific mechanisms in the regulation of the AP-1 family. These studies provide novel insights into the mediator-specific modulation of AP-1-regulated gene expression and the activation of MC in renal diseases.
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PMID:Gene, stimulus and cell-type specific regulation of activator protein-1 in mesangial cells by lipopolysaccharide and cytokines. 1085 36

We examined influences of estrogen and progestogen on gene expression of the growth regulatory molecules: platelet-derived growth factor (PDGF), interleukin-1 (IL-1), interleukin-6 (IL-6) and proto-oncogene c-myc in vascular smooth muscle cells (VSMC) by reverse transcription-polymerase chain reaction (RT-PCR) and Southern-blotting. VSMC were exposed to estrone-sulfate (E1-S) and medroxyprogesterone acetate (MPA) to induce differentiation. E1-S inhibited the expression of PDGF-A chain, IL-1, IL-6 and c-myc mRNA, whereas MPA had no effect. Inhibition by E1-S was not affected by treatment combined with MPA. These findings suggest that estrogen modulates these growth regulatory molecules and c-myc gene expression in VSMC but not progestogen. We concluded that estrogen may have a direct atheroprotective effect through inhibition of growth regulatory factors.
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PMID:Effect of estrogen and progesterone on gene expression of growth regulatory molecules and proto-oncogene in vascular smooth muscle cells. 1103 62

The rare benign extra-abdominal desmoid tumor is characterized by aggressive invasion of normal tissue. Treatment is complicated by its recurrence, invasiveness, and persistence. The etiology is unknown and the pathophysiology is obscure. Because of exuberant fibroblastic proliferation with collagenous tissue being the primary tissue component, this desmoid tumor has been compared with keloids arising from excessive scar formation in healing wounds. Numerous cytokines are associated with signaling for growth and maintenance of mesenchymal cells. Altered expression of these proteins is associated with many pathologic conditions. It has been proposed that the enhanced expression of platelet-derived growth factor and its receptor characterize desmoid tumors. We tested the hypothesis that the exuberant fibrosis of desmoid tumors may have resulted from the initiation of the cascade of molecular events producing increased expression of cytokines. We used immunohistochemical analysis of cytokines in desmoid tumors compared with keloids and skin to localize the expression of cytokines. The results showed localized increased expression of the cytokines epidermal growth factor, transforming growth factor-beta, tumor necrosis factor-alpha, vascular endothelial growth factor, interleukin-1beta, and interleukin-6 in the endothelial cells of blood vessels in the tumors. Production of tumor necrosis factor-alpha and interleukin-1beta in tumor tissue was increased, but we did not find increased expression of platelet-derived growth factor. We concluded that the increased expression of cytokines associated with angiogenesis usually found in wound healing and invasive tumors may contribute to the pathophysiology of the desmoid tumor.
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PMID:Cytokines associated with the pathophysiology of aggressive fibromatosis. 1105 3

Receptor for advanced glycation end-products (RAGE), and two of its ligands, AGE and EN-RAGEs (members of the S100/calgranulin family of pro-inflammatory cytokines), display enhanced expression in slowly resolving full-thickness excisional wounds developed in genetically diabetic db+/db+ mice. We tested the concept that blockade of RAGE, using soluble(s) RAGE, the extracellular ligand-binding domain of the receptor, would enhance wound closure in these animals. Administration of sRAGE accelerated the development of appropriately limited inflammatory cell infiltration and activation in wound foci. In parallel with accelerated wound closure at later times, blockade of RAGE suppressed levels of cytokines; tumor necrosis factor-alpha; interleukin-6; and matrix metalloproteinases-2, -3, and -9. In addition, generation of thick, well-vascularized granulation tissue was enhanced, in parallel with increased levels of platelet-derived growth factor-B and vascular endothelial growth factor. These findings identify a central role for RAGE in disordered wound healing associated with diabetes, and suggest that blockade of this receptor might represent a targeted strategy to restore effective wound repair in this disorder.
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PMID:Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. 1148 96


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