Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present evidence showing that TNF is capable of inducing an antiviral state in WISH cells thereby protecting them from the cytopathic effect of vesicular stomatitis virus. Establishment of the antiviral state requires pretreatment with TNF. Such pretreatment not only protects the cells in a dose-dependent manner, but it markedly reduces virus yield as well. Kinetic studies have shown that a pretreatment period as short as 4 h at 37 degrees C is effective in conferring protection. The antiviral activity of TNF could be attributed to the induction of IFN-beta. In fact, polyclonal antibodies to IFN-beta completely neutralized the antiviral state elicited by TNF. 2-5A synthetase activity was significantly enhanced when the cells were treated with doses of TNF that afforded antiviral protection. Finally, addition of specific antibodies to IFN-beta 2 (IL-6) during TNF pretreatment failed to abolish the antiviral state, thus suggesting that IFN-beta 2 is not involved in the TNF-induced antiviral state. Also, a homogeneous IFN-beta 2 preparation failed to exert antiviral activity in our cell system.
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PMID:The in vitro antiviral activity of tumor necrosis factor (TNF) in WISH cells is mediated by IFN-beta induction. 254 88

We find that pretreatment of WISH cells with tumor necrosis factor (TNF)-alpha, IL-1, and lymphotoxin/TNF-beta is capable of inducing an antiviral state in these cells, thereby protecting them from vesicular stomatitis virus cytopathic effect. Furthermore, we find that such a treatment causes a major inhibition of the synthesis of VSV proteins, as analyzed by SDS-PAGE. The 2-5A synthetase activity is also increased by treating the cells with doses of cytokines effective in antiviral protection. In this cell system, inclusion of polyclonal antibodies to IFN-beta during cytokine pretreatment abrogates the antiviral state elicited by the above cytokines, while antibodies to IFN-beta 2/IL-6 fail to abolish the cytokine-induced antiviral effects.
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PMID:Comparative study on the antiviral activity of tumor necrosis factor (TNF)-alpha, lymphotoxin/TNF-beta, and IL-1 in WISH cells. 254 53

The human beta 2 interferon (IFN-beta 2) gene, a gene that also codes for B cell differentiation factor 2 (BSF-2), plasmacytoma/hybridoma growth factor (HGF), and hepatocyte-stimulating factor (HSF), is expressed in a variety of lymphoid and nonlymphoid tissues. Endotoxin, or bacterial lipopolysaccharide (LPS) preparations derived from the outer membrane of Escherichia coli or Salmonella typhimurium rapidly elevate IFN-beta 2 mRNA level in human skin fibroblasts (FS-4 strain). E. coli-derived LPS enhances IFN-beta 2 mRNA expression in FS-4 fibroblasts at a concentration as low as 0.3 ng/ml; this response is near-maximal in the range of 0.1-1 microgram/ml LPS. The increase in IFN-beta 2 mRNA level caused by LPS in FS-4 cells is detected within 30 min after addition of LPS, is sustained for at least 20 h thereafter, appears to involve the protein kinase C signal transduction pathway, does not require new protein synthesis, and is inhibited by dexamethasone in a dose-dependent fashion (in the range 10(-6)-10(-8) M). Cultures of LPS-treated FS-4 cells exhibit an antiviral state against vesicular stomatitis virus, which can be prevented by anti-IFN-beta antiserum. Medium obtained from LPS-treated FS-4 cell cultures enhances the number of immunoglobulin-secreting cells in cultures of human B-lymphoblastoid (CESS) cells. Thus, LPS may trigger a number of host defense mechanisms in the course of infection due to Gram-negative bacteria by enhancing IFN-beta 2 production by the ubiquitous fibroblast.
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PMID:Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of beta 2 interferon by human fibroblasts. 282 51

Recombinant B cell stimulatory factor 2 (rBSF-2) did not display any detectable level of antiviral activity when using human diploid fibroblasts, DIP-2, FS-4, FS-7, amnion-derived WISH and FL cells with vesicular stomatitis virus (VSV) and Sindbis virus as challenging agents (less than 2.5 X 10(2) IU/mg). Furthermore anti-IFN-beta could not neutralize the immunoglobulin-inducing activity of BSF-2. Moreover anti-BSF-2 could not neutralize the antiviral activity of IFN-beta. The data indicate that BSF-2 is functionally and immunologically not related to IFNs.
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PMID:Absence of antiviral activity in recombinant B cell stimulatory factor 2 (BSF-2). 283 21

The expression in human fibroblasts of the beta 2-interferon (IFN-beta 2) gene, which is now recognized to be identical to the gene encoding B-cell differentiation factor BSF-2, is enhanced by several cytokines that affect cell growth (tumor necrosis factor, interleukin 1, platelet-derived growth factor, and beta 1-interferon). We have examined the possibility that IFN-beta 2 gene expression is regulated through activation, by diacylglycerol, of the protein kinase C pathway. The synthetic diacylglycerols 1,2-dioctanoylglycerol (diC8) and 1-oleoyl-2-acetylglycerol strongly enhanced IFN-beta 2, but not IFN-beta 1, gene expression in human fibroblasts (FS-4 strain). An increase in IFN-beta 2 mRNA level was detected within 15 min after addition of diC8 (290 microM) to FS-4 cells and was maximal approximately 20 hr later. An increase in IFN-beta 2 gene transcription was detected within 5 min of addition of diC8, and the rate of transcription was near-maximal by 15-30 min. The enhancement of IFN-beta 2 gene expression by diC8, interleukin 1, or tumor necrosis factor was not prevented by H8, a preferential inhibitor of cAMP- and cGMP-dependent protein kinases, but was blocked by H7, an inhibitor of protein kinase C as well as of cyclic nucleotide-dependent protein kinases. diC8 was found to protect FS-4 cells from the cytopathic effect of vesicular stomatitis virus; this protection was blocked by polyclonal or monoclonal antibodies that neutralize IFN-beta, suggesting that the antiviral effect was due to the secretion of IFN-beta 2 by the diC8-treated fibroblasts. The calcium ionophore A23187 (1-10 microM) also elicited an increase in the level of IFN-beta 2 mRNA in FS-4 fibroblasts; appropriate combinations of A23187 and diC8 had at least an additive effect in enhancing IFN-beta 2 mRNA levels. These results show that protein kinase C-activating or [Ca2+]-elevating agents rapidly increase the expression of the IFN-beta 2 gene in human fibroblasts.
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PMID:Rapid enhancement of beta 2-interferon/B-cell differentiation factor BSF-2 gene expression in human fibroblasts by diacylglycerols and the calcium ionophore A23187. 310 77

We have defined the expression of the mRNA for, and secretion of, IFN-beta 2/hepatocyte-stimulating factor/IL-6 (IFN-beta 2/IL-6) in human diploid fibroblasts (FS-4 strain) infected with different RNA- and DNA-containing viruses. RNA blot-hybridization analyses carried out 6-8 h after the beginning of infection showed that the RNA-containing Sendai virus (paramyxoviridae) enhanced IFN-beta 2/IL-6 mRNA levels 10-fold, followed, in decreasing order, by encephalomyocarditis (EMC, picornaviridae), vesicular stomatitis (VSV, rhabdoviridae), Newcastle disease virus (NDV, paramyxoviridae), and influenza A (Flu, myxoviridae) viruses. The DNA-containing pseudorabies virus (PR, herpesviridae) enhanced IFN-beta 2/IL-6 mRNA levels sixfold, while the effect of adenovirus type 5 (Ad5, adenoviridae) was considerably less and comparable with that of NDV or Flu. A rabbit antiserum raised against E. coli-derived human IFN-beta 2/IL-6 was used in immunoprecipitation experiments to monitor the secretion of 35S-methionine-pulse-labeled IFN-beta 2/IL-6 proteins by fibroblasts up to 7 h after the beginning of infection. Enhanced levels of secretion of IFN-beta 2/IL-6 (2-14-fold) were observed in every instance evaluated (Sendai, EMC, VSV, Flu, PR, Ad5 viruses). A biological consequence of enhanced secretion of IFN-beta 2/IL-6 was the ability of media from infected FS-4 cell cultures to enhance by 8-15-fold the synthesis and secretion of a typical acute phase plasma protein (alpha 1-antichymotrypsin) by human hepatoma Hep3B2 cells. These observations make it likely that IFN-beta 2/IL-6 mediates, in part, the host response to acute virus infections.
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PMID:Regulation of the acute phase and immune responses in viral disease. Enhanced expression of the beta 2-interferon/hepatocyte-stimulating factor/interleukin 6 gene in virus-infected human fibroblasts. 313 43

The hyper-IgD syndrome is a rare entity characterized by early onset of attacks of periodic fever. All patients have an elevated serum IgD (> 100 U/ml). Symptoms during attacks include joint involvements (arthralgias/arthritis), abdominal complaints (vomiting, pain, diarrhoea), skin lesions, swollen lymph nodes, and headache. In 1992 an International hyper-IgD study group was established, and to date the diagnosis has been made in 60, mainly European patients; 14 come from France. The disorder occurs in families and is transmitted by autosomal recessive inheritance. Linkage studies indicate that the gene encoding for familial Mediterranean fever is different from the gene for the hyper-IgD syndrome. In children the hyper-IgD syndrome should be distinguished from two other periodic febrile disorders. CINCA (chronic inflammatory, neurological, cutaneous and articular syndrome) and FAPA (periodic fever, adenopathies, pharyngitis, and aphtous stomatitis) share some symptoms with the hyper-IgD syndrome but in these syndromes serum IgD is normal. The pathogenesis remains to be elucidated but during attacks all patients have an acute-phase response with elevated C-reactive protein concentrations. During the febrile episodes, the inflammatory cytokines such as IL-6 TNF alpha, IFN gamma are increased together with natural occurring inhibitors such as IL-1ra and sTNFr. There is no therapy for the syndrome and patients will experience attacks during their entire life although frequency and severity tend to diminish with age.
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PMID:[Hyperimmunoglobulin D syndrome]. 756 50

A panel of long-term murine T lymphocyte clones specific for the glycoprotein of vesicular stomatitis virus (VSV) in association with either H-2I-Ad or I-E(d) was tested for the production of cytokines in both resting and poststimulation states using both in situ hybridization and bioassay. All but one of the clones showed antigen-specific cytolytic activity in a 4-hr 51Cr release assay. Unexpectedly, the clones did not appear to be typical Th1 cells. Five of these T cell clones produced both IL-2 and IFN-gamma but not IL-4 after stimulation with either phorbol 12-myristate 13-acetate (PMA) or concanavalin A (Con A). Some clones constitutively expressed mRNA for IL-2 and INF-gamma. The proliferation of these clones was factor independent, suggesting an autocrine growth mechanism. Three clones produced variable levels of IL-4 mRNA and some, to significant quantities, of IL-2 mRNA. One cytolytic clone produced neither IL-2 nor IL-4 mRNA to detectable levels, although mRNA for IFN-gamma was observed. A noncytolytic, Ag-specific clone produced IL-6, tumor necrosis factor (TNF), and lymphotoxin (LT), but no IL-2, IL-4, or IFN-gamma mRNA. There was a strong quantitative correlation between the expression of IL-2-, INF-gamma-, and LT-specific mRNAs by the clones. All the T cell clones tested which secreted INF-gamma and LT expressed no measurable IL-4 mRNA. We examined expression of several other genes in the panel of clones. These included TNF, met-enkephalin (met-enk), IL-1, and IL-6. IL-1 m-RNA synthesis was not observed in any of the T cell clones. Almost all clones produced TNF mRNA. Parallel bioassays showed that secreted IL-2/IL-4 activity levels and mRNA levels correlated well for all clones. Thus, we observed a great degree of heterogeneity among CD4+ cytolytic T lymphocyte clones.
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PMID:Lymphokine expression profile of resting and stimulated CD4+ CTL clones specific for the glycoprotein of vesicular stomatitis virus. 838 Oct 52

The ligand-binding subunit (gp80) of the human interleukin-6 receptor (IL-6R) was transiently expressed in COS-7 cells. The metabolically labeled protein was shown to be quantitatively released from the membrane within 20 h. We identified the protein released from the transfected COS-7 cells after purification to homogeneity and N-terminal sequencing as a soluble form of the gp80/IL-6R. Shedding of the gp80 protein was strongly induced by 4 beta-phorbol-12-myristate-13-acetate, indicating that the process was regulated by protein kinase C (PKC). This was further corroborated by the finding that co-transfection of a PKC expression plasmid led to enhanced shedding of the gp80 protein. Since shedding of gp80 could not be prevented by treatment of the cells with inhibitors of all known classes of proteases, a novel protease seems to be involved. As a control, an unrelated membrane protein (vesicular stomatitis virus glycoprotein) was transfected into COS-7 cells and analyzed for shedding. Since the turnover of this protein was not mediated by shedding, we conclude that the release of gp80 from COS-7 cells is a specific process. The shed gp80 protein specifically binds IL-6, and this complex shows biological activity on human hepatoma cells. Human peripheral blood monocytes released a soluble form of the gp80 protein into the culture medium upon PMA treatment indicating that PKC-regulated shedding is the physiological mechanism of generation of the soluble IL-6R.
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PMID:The soluble interleukin-6 receptor is generated by shedding. 843 81

Gene transfer into haematopoietic stem cells (HSC) has been investigated for treatment of genetic disorders, conferral of chemotherapy resistance and insertion of genes to inhibit HIV-1 replication. Methods have been available for almost a decade to transduce murine HSC using high-titre retroviral vectors and stimulation of HSC proliferation with cytokines such as IL-3 and IL-6. Unfortunately, attempts to replicate the high efficiency of gene transfer using canine or simian gene transfer/bone marrow transplantation models have consistently shown that only a small fraction (0.1-1%) of reconstituting HSC are transduced using protocols similar to those which are successful in murine models. Initial clinical trials using retroviral-mediated gene transfer into human HSC also produced minimal transduction frequencies. The dicotomous results may reflect differences in the cell cycle kinetics of murine HSC versus those of larger mammals or the density of receptors for the retroviral vectors on the cells. Attempts to increase the fraction of HSC which are in active cell cycle, a prerequisite for retroviral-mediated transduction, have used either combinations of recombinant cytokines, culture on marrow stromal layers, or alternative sources for HSC, such as mobilized peripheral blood stem cells or umbilical cord blood. Other efforts have used retroviral vectors packaged with either the Gibbon Ape Leukemia virus envelope or the Vesicular Stomatitis Virus G protein. To date, none of these methods has produced a significantly increased frequency of long-term reconstituting HSC. Results using adeno-associated virus (AAV)-based vectors for HSC transduction have been conflicting, with the stable persistence of non-integrated virus particles making interpretation of results difficult using in vitro assays. Therefore, clinical trials may best be directed toward disorders that may benefit from a small fraction of genetically corrected HSC. These would include disorders where progeny of corrected HSC would be expected to have a selective survival advantage (e.g. SCID, WAS, HIV, chemoresistance) or where a small fraction of corrected cells can have a direct clinical benefit (e.g. CGD, MPS). Further basic research into HSC biology and gene delivery vectors must continue for wider application, such as haemoglobinopathies and some lysosomal storage diseases.
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PMID:Gene therapy for haematopoietic and lymphoid disorders. 902 Sep 37


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