UNIPROT:P05231 - FACTA Search

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

The "stromal" or adherent cells of long-term murine Dexter explant bone marrow cultures provide the best in vitro model of the bone marrow microenvironment. Colony-stimulating factor-1 (CSF-1) is produced constitutively by these cells and is easily detected, but most investigators have not found constitutive production of the other hemolymphopoietic cytokines. We have previously reported the detection of granulocyte-macrophage-CSF (GM-CSF) in murine stromal cultures and its induction by the lectin Pokeweed mitogen. The present studies analyzing stromal cytokine messenger RNA (mRNA) production by standard Northern blot analysis show constitutive production of mRNAs for CSF-1, GM-CSF, granulocyte-CSF (G-CSF), c-kit ligand (KL), and interleukin-6 (IL-6), but not IL-3, IL-4, or IL-5 by 3-week irradiated or nonirradiated murine Dexter stromal cells. Exposure of stromal cells to Pokeweed mitogen or IL-1 16 hours before RNA harvest induces the messages for GM-CSF, G-CSF, KL, and IL-6, but not IL-3, IL-4, IL-5, or CSF-1. Polymerase chain reaction amplification of cDNA made with reverse transcriptase from stromal RNA using two separate sets of IL-3-specific primers shows the presence of IL-3 message in irradiated stromal cells, which is only detectable with this more sensitive technique. The factor-dependent cell lines FDC-P1 and 32D are supported by the stromal cells without the addition of exogenous growth factors, demonstrating a cytokine activity in these cultures that is inhibited by the addition of anti-IL-3 or anti-GM-CSF antibodies. These data indicate that murine Dexter stromal cells constitutively produce CSF-1, GM-CSF, G-CSF, IL-6, KL, and IL-3. This growth factor production could explain the support of granulocyte, macrophage, and megakaryocyte production and stem cell maintenance in Dexter-type long-term murine bone marrow cultures.
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PMID:Biologic significance of constitutive and subliminal growth factor production by bone marrow stroma. 137 43

A porcine interleukin-6 (pIL-6) cDNA has been cloned from pig spleen cDNA library to provide information that would allow us to study IL-6 mRNA expression during pregnancy of several domestic Artiodactyla. The cDNA is 1058 bp long and with a single open reading frame that encodes a 212 amino acid polypeptide with 28-residue signal sequence. It shares 61% and 43% amino acid sequence identity with human and mouse IL-6, respectively. PCR procedures with primers designed from regions of sequence conserved between human and pig have been used to identify IL-6 cDNA in lambda gt11 libraries constructed from day 15-16 (sheep), day 17 (cattle), and day 13-17 (pig) conceptus mRNA. The presence of IL-6 mRNA in elongating preimplantation ovine (days 13-25), porcine (days 13-21), and bovine (days 16-20) conceptuses was also demonstrated by PCR after reverse transcription of total ribonucleic acid with reverse transcriptase and by solution hybridization with a pIL-6 cRNA probe. These observations suggest that IL-6 is a product of these early conceptuses and may be involved in early maternal responses to the presence of an embryo within the uterus.
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PMID:Expression of interleukin-6 in porcine, ovine, and bovine preimplantation conceptuses. 149 80

Uterine stromal (USC) and uterine epithelial (UEC) cells were isolated from immature and mature mice to determine their ability to secrete interleukin-6 (IL-6) in response to ovarian steroids, IL-1 alpha, and soluble products produced by the heterologous cell type. In addition, the effect of IL-6 on embryo attachment and outgrowth in vitro was determined. UEC cultured on nitrocellulose filter inserts in a polarized manner secreted IL-6 with a 2.5- to 5-fold apical vs. basal preference, as determined by a B9 hybridoma cell proliferation assay and enzyme-linked immunosorbent assay. The hormonal status of animals at the time uteri were removed did not influence subsequent secretion of IL-6, as UEC isolated from immature, diestrous, and estrous stage mice exhibited both a similar amount and had a similar apical preference for secretion of IL-6. The addition of 17 beta-estradiol (E) to UEC cultures markedly inhibited total IL-6 secretion, but did not affect vectorial secretion. The inhibitory effect of E on IL-6 secretion by UEC was consistent with an apparent decrease in IL-6 transcript observed by a reverse transcriptase polymerase chain reaction assay. Other transcripts detected by this assay in UEC included IL-1 alpha, but not IL-1 beta or tumor necrosis factor-alpha. Secretion of IL-6 by UEC was not stimulated by IL-1 alpha, conditioned medium from USC, or coculture with USC. USC secreted IL-6, and while this also was inhibited by E, progesterone was more effective in this regard at physiological concentrations. In addition, there was a synergistic effect of E plus progesterone on inhibition of IL-6 secretion by USC. Secretion of IL-6 by USC was stimulated by IL-1 alpha, and coculture studies demonstrated the ability of UEC to stimulate a several-fold increase in IL-6 secretion by USC. The cytokine transcripts detected in USC cultures included IL-6 and IL-1 alpha, but not IL-1 beta. Transcripts for tumor necrosis factor-alpha were present in USC only after culture with IL-1 alpha. IL-6 added to blastocysts on laminin-coated tissue culture wells resulted in a transient inhibition of the rate of blastocyst attachment and, to a greater extent, an inhibition of the rate of embryo outgrowth. In addition, IL-6 inhibited the size of embryo outgrowths at 24 and 48 h of culture.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Secretion and hormonal regulation of interleukin-6 production by mouse uterine stromal and polarized epithelial cells cultured in vitro. 150 48

We have used the reverse transcriptase-polymerase chain reaction technique to gain insight into the pathogenesis of encephalitis caused by Borna disease virus (BDV). RNA specific for BDV was first detected in the olfactory bulb of intranasally infected rats at 6 days postinfection (p.i.). At 14 days p.i., high levels of BDV RNA were found in all brain regions, and at 26 days p.i., BDV-specific RNA was also present in the eye, nasal mucosa, and facial skin. In the chronic phase of the disease, BDV RNA was identified in many peripheral organs but not in blood. Analysis of brain tissue for the presence of cytokine mRNAs revealed that the mRNA levels of interleukin-6 (IL-6), tumor necrosis factor alpha, and IL-1 alpha had increased sharply at 14 and 26 days p.i. These cytokine mRNAs reached maximum levels at the peak of inflammatory reactions and decreased drastically in the chronic phase of the disease. Although IL-2 mRNA was also found in normal brain, it was markedly increased in BDV-infected brain at 14 days p.i. Expression of gamma interferon (IFN-gamma) mRNA, which was not observed in normal rat brain, was detected at 14 days p.i. and reached a maximum level at 38 days p.i. IL-2 and IFN-gamma mRNA expression correlated with expression of CD4 and CD8 mRNAs, indicating that both CD4+ and CD8+ T lymphocytes are induced in the early stages of BDV infection. Since IFN-gamma and CD8 mRNA levels were still highly elevated in the chronic phase of Borna disease, it is likely that CD8+ T lymphocytes act to reduce inflammation and to ameliorate neurological signs during the chronic phase of infection.
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PMID:Kinetics of virus spread and changes in levels of several cytokine mRNAs in the brain after intranasal infection of rats with Borna disease virus. 173 Nov 17

Human promonocyte cells chronically infected with human immunodeficiency virus type (HIV-1) (clone U1.1.5) were grown in the presence of media conditioned by human astrocytes and glioma cell lines U251 and 253. HIV-1 expression was assessed by measuring reverse transcriptase activity. All media conditioned by unstimulated and lipopolysaccharide (LPS) stimulated glial cells induced HIV-1 expression and contained detectable levels of interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-alpha). An antibody against IL-6, but not against TNF-alpha, reduced the induction of HIV-1 by the conditioned media in a concentration-dependent manner. The magnitude of HIV-1 induction by the conditioned media was proportional to the concentration of IL-6 in them. The data indicate that normal and transformed human astrocytes are capable of stimulating HIV-1 expression in chronically infected promonocytic cells by secreting IL-6. The results demonstrate that cytokines secreted by neural cells could play an important role in regulating HIV-1 expression in the brain.
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PMID:Human astrocytes stimulate HIV-1 expression in a chronically infected promonocyte clone via interleukin-6. 174 78

The expression and biological function of interleukin-6(IL-6), and its receptor mRNA, were studied in a human megakaryocytic cell line (CMK). IL-6 possessed stimulatory effects on the DNA synthesis as well as colony formation of CMK cells. The IL-6 receptor mRNA could be detected by the method of reverse transcriptase polymerase chain reaction (RT-PCR) but not Northern blotting. On the contrary, IL-6 mRNA was detected by the method of RT-PCR, and its expression induced by the addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) could be clearly shown by Northern blotting. These findings indicate that IL-6 and its receptor mRNA should be analyzed by both methods, and the growth and differentiation of CMK cells may be controlled by an IL-6 autocrine loop. Next, the expression and biological role of low molecular GTP-binding proteins (smg p21A and -B) mRNAs were examined in CMK cells. Both the smg p21A and -B mRNAs were detected in CMK cells using Northern blotting, and their levels were markedly elevated by TPA treatment. The mRNA level of glycoprotein IIb, a typical marker of the megakaryocytes, was increased by TPA, but the time course of the increase in the smg p21 mRNA levels was more rapid that that in the GPIIb mRNA level. These findings suggest that smg p21s play an important role during the TPA-induced differentiation of CMK cells.
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PMID:[Expression and detection of platelet specific genes in human megakaryocytic cells]. 177 68

Monocytes treated with interferon-alpha (IFN-alpha) at virus challenge show no evidence of human immunodeficiency virus (HIV) infection: no p24 antigen or reverse transcriptase (RT) activity, no viral mRNA and no proviral DNA. Levels of p24 antigen and RT activity in monocytes infected with HIV 1-3 weeks before IFN-alpha treatment gradually decrease to baseline. HIV-induced cytopathic changes are markedly reduced, as are levels of HIV mRNA: the frequency of productively infected cells is less than or equal to 1%. But, levels of proviral DNA in the IFN-alpha-treated and control HIV-infected cells are indistinguishable, and remain so through 3 weeks. Large quantities of proviral DNA in IFN-alpha-treated cells with little active transcription suggest true microbiological latency. The major potential source for IFN-alpha in HIV-infected patients is the macrophage. With any of 15 virus isolates, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, IFN-omega or IFN-beta are not detected nor the mRNA expressed in HIV-infected or uninfected monocytes. Both uninfected and HIV-infected monocytes produce high levels of these cytokines after treatment with synthetic double-stranded RNA (poly-I:C). Uninfected monocytes also produce high levels of IFN-alpha after treatment with Poly-I:C, Newcastle disease virus or herpes simplex virus. In marked contrast, HIV-infected monocytes express no IFN-alpha activity or mRNA before or after treatment with any of these agents. The markedly diminished capacity of HIV-infected monocyte to produce IFN-alpha reflects a specific transcriptional block and may be an adaptive mechanism of virus to alter basic microbicidal functions of this cell.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of cytokine and viral gene expression in monocytes infected with the human immunodeficiency virus. 188 15

Castleman's disease (CD) is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes. CD may be localized or multifocal, and is often associated with signs and symptoms of generalized inflammation. The systemic manifestations of CD have been previously attributed to an overproduction of interleukin-6 (IL-6) by the tumor, although there is evidence that IL-6 is not responsible for all of the symptoms. We describe a 9-year-old boy who developed Castleman's disease with systemic findings of hypochromic microcytic anemia, growth arrest, inflammation, and hyperimmunoglobulinemia. Following surgical resection, all of the symptoms and laboratory abnormalities resolved. Using reverse transcriptase polymerase chain reaction (RT-PCR) analysis of the tumor, we found elevated levels of IL-6 mRNA as expected, but also elevated levels of tumor necrosis factor beta (TNF-beta) and gamma interferon (gamma-IFN) mRNA. Because these cytokines are mediators of immune regulation and inflammation, we propose that TNF-beta and gamma-IFN also play an important role in the pathophysiology of Castleman's disease.
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PMID:Elevated levels of tumor necrosis factor-beta, gamma-interferon, and IL-6 mRNA in Castleman's disease. 749 11

In the present work we explored cellular sites of interleukin-6 (IL-6) biosynthesis in human follicular aspirates from patients undergoing in vitro fertilization therapy and the effects of this cytokine on oocyte fertilization and granulosa cell (GC) steroidogenesis. Biological IL-6 activity from 20-40 IU/mL was present in follicular fluids from 22 patients; it was also detected in 10 of 22 supernatants of cultured oocyte-cumulus complexes and in cumulus cell and GC cultures. Biological IL-6 activity in oocyte-cumulus complex cultures was not related to fertilization rates. Total ribonucleic acid was isolated from follicular aspirates and GC-enriched preparations. After reverse transcriptase and polymerase chain reaction cycles using oligonucleotide primers corresponding to known cDNA sequences for IL-6, a 126-basepair band characterized the amplification product of IL-6 transcripts on gel electrophoresis. To localize IL-6 messenger ribonucleic acid, in situ hybridization analysis was performed using a [35S]IL-6 riboprobe. The distribution of transcripts was more dense (15% vs. 3% stained cells) in GC-enriched preparations, which contained more than 95% GCs, than in original follicular preparations, which contained 20-40% viable GCs; it was not significantly modified by the presence of macrophage contaminants. The expression of IL-6 protein was assessed by positive immunohistological stainings. Biological IL-6 activity was higher, and in situ hybridization signals were more dense and more intense in 24-h GC cultures than in 72-h GC cultures, suggesting that IL-6 biosynthesis was transiently induced. Under experimental conditions of low IL-6 endogenous levels in cultures, adding recombinant human IL-6 from 10-200 IU/mL had no effect on progesterone production or aromatase activity in GC cultures free of macrophages, whereas in GC cultures including macrophage contaminants, stimulatory effects on basal and hCG-stimulated progesterone production and on basal and FSH-stimulated aromatase activities were observed. The present study provides strong support for the view that IL-6 is produced by GCs in the preovulatory follicle at the time of ovulation. In addition, we showed that IL-6 might be an intraovarian regulatory factor concerned with steroidogenesis.
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PMID:Interleukin-6 biosynthesis in human preovulatory follicles: some of its potential roles at ovulation. 751 93

The ability of grifolan (GRN), a purified fungal (1-->3)-beta-D-glucan, to induce various cytokines from macrophages was examined in vitro. Interleukin-6 (IL-6) activity in supernatants from the culture of macrophage cell line, RAW264.7 was dependent on increasing doses of GRN. The level of IL-6 induced with 500 micrograms/ml of GRN was comparable to that induced with lipopolysaccharide (LPS) 10 micrograms/ml. Enhancement of the mRNA level of IL-6 by treatment with GRN was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The effect of GRN on production of IL-6 was also observed using peritoneal macrophages from C3H/HeJ mice which did not respond to endotoxins. This data suggested that the ability of GRN to activate IL-6 production of macrophages is not due to contamination of endotoxins in the preparation. Enhanced production of cytokine by GRN was observed not only with IL-6, but also with interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). In the production of TNF alpha, GRN was more effective than LPS used in this study. Other soluble or gel-forming(1-->3)-beta-D-glucans from various sources did not enhance the production of such cytokines although they are structurally similar to GRN. The above results indicate that GRN is a novel macrophage activator which augments cytokine production without dependence on endotoxins.
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PMID:Enhancement of cytokine production by macrophages stimulated with (1-->3)-beta-D-glucan, grifolan (GRN), isolated from Grifola frondosa. 753 72

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