Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-6 is one of the most well-characterized cytokines with pleiotropic properties. Besides its B-lymphocyte activation role in hematopoiesis, interleukin-6 plays a central role in regulation of systemic inflammation. Interleukin-6 binds to receptors on target cells (such as hepatocytes and lymphocytes), consisting of an 80 kDa binding chain and gp130, a polypeptide responsible for signal transduction. In addition to the detection of elevated amounts of interleukin-6 in the blood, gene expression (mRNA) of subunits of the interleukin-6 receptor complex have also been studied by examining the reverse transcriptase polymerase chain reaction on peripheral lymphocytes from patients with characteristic radiological symptoms suffering from Crohn's disease. Our data show significantly elevated gene expression both of the 80 kDa interleukin-6 binding chain and gp130. These results suggest that enhancement of the expression of the constituents of interleukin-6 and the interleukin-6 receptor system plays a relevant role in systemic inflammation in inflammatory bowel disease.
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PMID:Increased interleukin-6 levels, interleukin-6 receptor and gp130 expression in peripheral lymphocytes of patients with inflammatory bowel disease. 986 12

Receptors for interleukin-6 (IL-6) occur in body fluids in soluble form, as well. This is an approx. 50 kDa protein with the ability to bind IL-6. The soluble IL-6 receptor (sIL-6R)/IL-6 complex can attach to membrane anchored gp130, a molecule associated with the signal transduction induced by IL-6 and by other related cytokines. Earlier we described the appearance of sIL-6R in various body fluids of autoimmune patients. In this study using reverse transcriptase polymerase chain reaction (RT-PCR) we isolated and characterised a truncated form of amplified cDNA reverse-transcribed from IL-6 receptor mRNA both from human hepatoma cell line HepG2 and mononuclear cells from inflammatory bowel disease (IBD) patients. Using digestion by Pvu II restriction endonuclease and direct nucleotide sequencing we conclude that alternative splicing is likely involved in generation of sIL-6R. Our further experiments suggest that IL-6 and recombinant sIL-6R themselves do not influence the alternative splicing of IL-6 receptor gene.
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PMID:Generation of 'truncated' interleukin-6 receptor (IL-6R) mRNA by alternative splicing; a possible source of soluble IL-6R. 1039 66

Cell-cell contact of myeloma-derived cell lines (MDCL) or fresh myeloma cells with bone marrow stromal cells (BMSC) is known to induce interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1) production by a marrow stromal cell line. To determine if other BMSC transcripts are altered during cell-cell contact between BMSC and tumor cells, we have used cell lines ARH77 and U266 in an in vitro model. Using mRNA differential display and reverse transcriptase-polymerase chain reaction (RT-PCR), it was determined that a total of 141 transcripts were either upregulated or downregulated in the BMSC on contact with cell membrane from cell lines ARH77 and U266. Induction of two of these transcripts, interleukin-6 (IL-6) and gp130 in the BMSC by ARH77 cell membranes was studied in greater detail. Real-time PCR was used to quantitate transcript levels of gp130, IL-6, and 36b4, a housekeeping gene. Cycloheximide (CHX) alone increased both gp130 and IL-6 transcripts in the BMSC. In addition, CHX caused a superinduction of these transcripts in BMSC exposed to ARH77 cell membranes. The induction of gp130 was independent of the increase in IL-6 mRNA. Upregulation of gp130, a component of the membrane receptors for the IL-6 superfamily, can have profound effects on the response of BMSC to the IL-6 superfamily of cytokines.
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PMID:Acute activation of gp130 gene expression in bone marrow stromal cells by contact with myeloma-derived lymphoblastic cell line ARH77 cell membranes. 1133 Oct 38

Removal of the synaptic targets of olfactory receptor neurons by olfactory bulb ablation results in apoptosis of olfactory receptor neurons and up-regulation of proliferation of their progenitors. This study focuses on the expression of the neuropoietic cytokines leukemia inhibitory factor (LIF) and its receptor (LIFR) and interleukin 6 (IL-6) and its receptor (IL-6R) in intercellular signaling pathways in the olfactory mucosa after target ablation. Olfactory bulbectomy (OBX) resulted in several transient, early-onset, temporally integrated events that were detected immunohistochemically. Macrophages infiltrated the olfactory epithelium (OE) by 16 hours post-OBX. LIF expression was up-regulated transiently at 2 days post-OBX, when up-regulated expression of LIFR also was detected on globose basal cells (GBCs), a subpopulation of which are immediate progenitors of olfactory receptor neurons. GBC proliferation peaked at 3--4 days post-OBX. In the olfactory nerve (ON), LIF-positive and IL-6-positive macrophage infiltration was followed by the transient up-regulation of expression of LIFR, IL-6, and IL-6R in ensheathing cells by 3 days post-OBX. The mRNAs for LIF/LIFR, IL-6/IL-6R, and their common signal-transduction molecule, gp130, in olfactory-nasal mucosa from control mice and from 3-day post-OBX mice were detected with reverse transcriptase-polymerase chain reaction (RT-PCR). Analysis of Northern blot and relative quantitative RT-PCR demonstrated similar temporal patterns of changes in relative mRNA levels for both LIF and IL-6, which were up-regulated by 16 hours post-OBX and peaked at 2--3 days post-OBX. These data indicate that LIF from infiltrating macrophages acts as a mitogen for GBCs and that LIF from infiltrating macrophages and IL-6 from infiltrating macrophages and ensheathing cells act as repair factors in the ON.
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PMID:Leukemia inhibitory factor, interleukin-6, and their receptors are expressed transiently in the olfactory mucosa after target ablation. 1137 11

Mast cell hyperplasia is observed in various inflammatory skin diseases. Although the mechanisms involved in the pathogenesis of these conditions remains largely uninvestigated, it is speculated that mediators produced in the lesional skin provide a favorable microenvironment for mast cell growth. Among the proinflammatory mediators, leukemia inhibitory factor (LIF), which shares a receptor component (gp130 subunit) with interleukin-6 (IL-6), has been identified as a mast cell growth-enhancing factor produced by cells of the keratinocyte-derived cell line (KCMH-1). In this study, we investigated the effect of four IL-6 family cytokines, IL-6, IL-11, oncostatin M (OSM) and LIF on mast cell growth in a mast cell/fibroblast co-culture system. When mouse bone marrow-derived cultured mast cells (BMMC) were maintained on a NIH/3T3 fibroblast monolayer, these cytokines induced proliferation of the mast cells, but none of the cytokines had any effect on mast cell proliferation in the absence of fibroblasts. mRNA for gp130 and receptors for the four IL-6 family cytokines were detected in NIH/3T3 fibroblasts by reverse transcriptase-mediated polymerase chain reaction. In contrast, only mRNA for the IL-11 receptor and gp130 were detected in BMMC. Tyrosine phosphorylation of gp130 was observed in NIH/3T3 fibroblasts after stimulation with all the cytokines. Some IL-6 family cytokines enhanced the production of stem cell factor (SCF), a potent mast cell growth factor, from NIH/3T3 fibroblasts, but the amount of SCF produced by NIH/3T3 fibroblasts was not paralleled by the mast cell growth-enhancement induced by the IL-6 family cytokines. When anti-SCF antibody was added with the IL-6 family cytokines in the BMMC/fibroblast coculture system, a significant effect of these cytokines remained, although the growth-enhancing activity was markedly reduced. A similar result was obtained when BMMC were prepared from W/W(V)-mice, which lack functional c-kit, in the BMMC/ fibroblast coculture system. These results suggest that IL-6 family cytokines stimulate mast cell growth by a fibroblast-dependent mechanism, and also suggest the existence of another pathway between BMMC and NIH/3T3 fibroblasts cooperating with the SCF/c-kit pathway. IL-6 family cytokines may thus contribute to mast cell hyperplasia in skin diseases.
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PMID:The IL-6 family cytokines, interleukin-6, interleukin-11, oncostatin M, and leukemia inhibitory factor, enhance mast cell growth through fibroblast-dependent pathway in mice. 1182 Jul 27

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints. This review discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years; increased gp130, which is a neutrophil cytokine transducing protein; increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and IL-1 beta, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia. In addition, this review describes the mechanism by which alterations in cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and the influence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively. The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.
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PMID:Fibromyalgia, hepatitis C infection, and the cytokine connection. 1294 86

There is a growing recognition of choroid plexus functioning as a source of neuropeptides, cytokines and growth factors in cerebrospinal fluid (CSF) with diffusional access into brain parenchyma. In this study, choroid plexus and other components of the CSF circulatory system were investigated by Western blotting, reverse transcriptase polymerase chain reaction and immunohistochemistry for production of interleukin-6-related cytokines characterized by neuroactivity [cardiotrophin-1 (CT-1), ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin M] and signaling through the gp130/leukemia inhibitory factor receptor-beta receptor heterodimer. Western blot analysis showed that CT-1 was the only cytokine family member detectable in adult rat choroid plexus, as in leptomeninges. The specificity of detection was verified with blots of the same tissues from CT-1-deficient mice. Levels of both CT-1 mRNA and protein were constitutively high in rat from birth through adulthood in choroid plexus, up-regulated postnatally in leptomeninges and undetectable in brain parenchyma. Using antigen retrieval, CT-1 immunolocalized to choroid epithelial cells in all choroid plexuses in addition to leptomeninges (arachnoid and pial-glial membranes). Ependymal cells lining the ventricular neuroaxis, unlike the central canal, were also CT-1-immunoreactive. Western blots indicated rat choroid epithelial cells express and release CT-1 immunoreactivity under defined culture conditions and also revealed the presence of a CT-1-like protein in human choroid plexus and CSF. Previously, CT-1 has been conceptualized to function as a target-derived factor for PNS neurons. Our study clearly demonstrates production of CT-1 in the postnatal and adult CNS, specifically by cell types comprising the blood-CSF barrier, and its accumulation in ventricular ependyma. This finding has broad implications for CT-1 functioning apart from other leukemia inhibitory factor receptor ligands as a CSF-borne signal of brain homeostasis, one possibly involving regulation of the barrier itself, the ependyma or target cells in the surrounding parenchyma, including the subventricular zone. A rationale for studies examining CT-1-deficient mice in these respects is provided by the data.
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PMID:Cardiotrophin-1 in choroid plexus and the cerebrospinal fluid circulatory system. 1521 67

Pro-inflammatory cytokines, in addition to their role in host defence, can be considered a disease mediator; therefore, a reduction in cytokine synthesis or its effects is becoming a target of many diseases. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that could play a role in several clinical problems related to dialysis treatment. Biological activities of IL-6 could be modulated by two soluble circulating receptors, namely sIL-6R and sgp130. sIL-6R can enhance the inflammatory effects of IL-6 and; therefore, is an "agonistically" acting molecule. On the contrary, sgp130 efficiently binds the IL-6/sIL-6R complex with "antagonistic" effects. In this study we evaluated sgp130 release by peripheral blood mononuclear cells (PBMC) harvested from 10 healthy controls (CON) and 11 end-stage renal disease (ESRD) patients undergoing renal dialysis therapy RDT) with cellulosic hemophan membrane (HD). We also evaluated gp130 gene expression by reverse transcriptase polymerase chain reaction (RT-PCR). gp130 is the membrane bound receptor of IL-6 that could be proteolytically cleaved to generate soluble sgp130. Our results demonstrated that HD. at basal conditions, showed a higher release of sgp130 as compared with CON. We also demonstrated by RT-PCR at basal conditions a higher gene expression of gp130 in HD, as compared with CON. These results took place in the absence of any mitogenic stimulation and suggest that in HD patients an inflammatory subclinical status increases sgp130 release. The results obtained after lipopolysaccharide (LPS) stimulation confirm the role of inflammation on the increased release of sgp130 in HD patients.
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PMID:[The IL-6 soluble receptors in hemodialyzed patients]. 1574 93


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