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)

Porcine interferon (POIFN)-alpha prepared in primed peripheral blood leukocyte cultures induced with Newcastle disease virus and POIFN-beta from PK-15 cell cultures induced with polyinosinic:polycytidylic acid were partially purified by precipitation with potassium thiocyanate and anion exchange chromatography. Mean purification factors in terms of units of POIFN per mg of protein, of 37 and 12 were obtained for POIFN-alpha and POIFN-beta respectively. In yield reduction assays in swine testis and pig kidney cell cultures, POIFN-alpha and POIFN-beta had greater antiviral activity against vesicular stomatitis virus than against transmissible gastroenteritis virus (TGEV). The antiviral effects were greater at higher concentrations of interferon (IFN), and when the IFN treatments were continued postinfection. Porcine interferon-beta showed greater antiviral activity against TGEV than POIFN-alpha, but this may have been partly due to cytotoxicity. There were no major differences in the antiviral activities of crude and partially purified IFN preparations. Both types of IFN showed antiviral activity against TGEV in yield reduction assays in porcine intestinal explant and intestinal epithelial cell cultures. Crude POIFN-beta was found to be rapidly cytotoxic, especially in porcine cells, and some fractions of partially purified POIFN-beta were also cytotoxic. The cytotoxicity of POIFN-beta was partially neutralized by antibodies against human IFN-beta, but human IFN-beta was not cytotoxic for porcine or bovine cells.
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PMID:Antiviral activity against transmissible gastroenteritis virus, and cytotoxicity, of natural porcine interferons alpha and beta. 165 3

We have previously shown that the antiviral state of explanted mouse peritoneal macrophages (PM) decays during in vitro culture and that this decay is much more rapid in Lpsd PM than it is in Lpsn PM. Moreover, Lpsn PM can transfer the antiviral state to other cells, whereas Lpsd PM cannot. In vitro treatment of Lpsn PM with different agents [i.e., bacterial lipopolysaccharide (LPS), interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, macrophage colony-stimulating factor (M-CSF) and antibody to Mac-1 antigen] induced an antiviral state to vesicular stomatitis virus (VSV) which was inhibited by antibodies to IFN-beta. Treatment of Lpsn PM with LPS or IFN-gamma resulted in greater accumulation of IFN-beta mRNA, whereas no change in the barely detectable levels of IFN-alpha mRNA was observed. Marked accumulation of IFN-beta mRNA was also observed in PM after TNF-alpha treatment. M-CSF and IFN-gamma (but not LPS) also induced an IFN-mediated antiviral state in Lpsd PM. Low levels of spontaneous transcription of IFN-beta mRNA were detected in nuclei from Lpsd PM. Treatment of Lpsd PM with IFN-gamma for 3 h resulted in the accumulation of IFN-beta mRNA without any concomitant increase in the transcription of the IFN-beta gene, as determined by run-on transcription assays with isolated nuclei. The addition of as little as I international unit/ml of IFN-gamma to PM resulted in a 100-fold inhibition of VSV yield. As antibodies to IFN-alpha/beta inhibited only a portion of the IFN-gamma-induced antiviral state, such an antiviral state might reflect the synergism between IFN-gamma and endogenous IFN-beta. In fact, the addition of low doses of both IFN-gamma and IFN-beta to either Lpsn or Lpsd PM resulted in synergistic antiviral effects. In vivo treatment of Lpsd mice with granulocyte-macrophage (GM)-CSF, M-CSF, IFN-gamma or Newcastle disease virus rendered peritoneal cells capable of transferring an antiviral state. These results indicate that (i) various stimuli can induce IFN-beta production by PM, (ii) Lpsd PM spontaneously transcribe low levels of IFN-beta mRNA, even though they cannot transfer an antiviral state, (iii) different stimuli, but not LPS, induce a normal IFN response in Lpsd PM, (iv) IFN-gamma increases the accumulation of IFN-beta mRNA in Lpsd PM by post-transcriptional mechanisms and (v) IFN-gamma may act synergistically with endogenous IFN-beta in inducing a potent antiviral state to VSV in PM.
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PMID:Effects of different biological response modifiers on interferon expression in bacterial lipopolysaccharide (LPS)-responsive and LPS-hyporesponsive mouse peritoneal macrophages. 170 75

We are exploring the use of interferon (IFN) genes for somatic cell gene therapy and have investigated the possibility of transforming cells into low constitutive IFN producers over prolonged periods of time without impeding cell survival or replication. Here we report the possibility of conferring a permanent antiviral state to cells by introducing an IFN-beta gene with a modified transcriptional control. This was achieved by placing the murine IFN-beta-coding sequence behind the IFN-inducible 0.6-kb XhoII-NruI promoter region of the H-2Kb major histocompatibility complex gene. BALB/c 3T3 cells that are normally permissive for virus infection were transformed with this construction, and 14 of the 21 clonal cell lines obtained displayed different levels of enhanced resistance to the replication of vesicular stomatitis virus, encephalomyocarditis virus, and Semliki Forest virus. The permanent antiviral state was dependent on the presence of new IFN-beta fragments in Southern blots and was accompanied by very low constitutive synthesis of IFN-beta, and the presence of construct-derived IFN mRNA could be demonstrated only after polymerase chain reaction amplification of cDNA. The antiviral state was stable over a 9-month period in culture, corresponding to about 250 cell generations, and did not affect cell replication, since the average population doubling time of these cells was not significantly different from that of the control clone. Twenty-nine control clonal cell lines, stably transformed with either the neo gene alone (22 lines) or the neo gene together with a mutated murine IFN-beta gene coding for an inactive protein (7 lines), did not develop stable antiviral expression. We conclude that low constitutive synthesis of autocrine IFN-beta is sufficient to induce a permanent antiviral state, is compatible with cell survival and replication, and therefore merits further exploration for use in somatic cell gene therapy.
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PMID:Stable antiviral expression in BALB/c 3T3 cells carrying a beta interferon sequence behind a major histocompatibility complex promoter fragment. 184 90

CTL-mediated selection for loss of expression of Mta by H-2-heterozygous SV40-transformed mouse fibroblasts (line 24SV) produced an unusual phenotypic class of maternally transmitted Ag negative mutants defective in both MHC expression and in anti-viral activity. Severely reduced surface expression of class I MHC Ag from multiple loci of both haplotypes correlated with low levels of MHC H chain and beta 2-microglobulin mRNA. Inasmuch as IFN can up-regulate class I expression and some fibroblasts elaborate autocrine IFN-beta, we examined whether IFN could restore wild-type expression of class I MHC Ag. However, IFN could not restore wild-type expression. Moreover, the fold-increases in class I Ag and mRNA expression were significantly reduced in mutant cells compared to wild-type cells. These results suggested that the mutants might have generalized defects in IFN response. Inasmuch as the induction of an anti-viral state is a hallmark of IFN responses, we exposed cells to IFN-alpha, -beta, or -gamma and challenged with virus. 24SV cells, exposed to any of the three IFNs, were completely protected from destruction by vesicular stomatitis, mengovirus or respiratory syncytial viruses. In contrast, MHC and anti-viral defective mutants could not be protected from virus-induced lysis by any IFN. Somatic cell hybridization analyses indicated that both basal MHC and IFN-inducible phenotypes were recessive to wild-type, and that a trans-acting regulatory factor required for basal MHC expression is defectively expressed in the mutants. Such a factor may integrate the organismal response to virus infection, encompassing both immune and nonimmune anti-viral responses.
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PMID:Mutational analysis of regulation of MHC and anti-viral genes. 184 75

Equine interferon-beta 1 (EqIFN-beta 1) was purified from extracts of recombinant Escherichia coli by sequential chromatography on hydroxylapatite, anion-, and cation-exchangers. The resulting protein was greater than 98% pure as determined by sodium dodecylsulfate gel electrophoresis, gel permeation HPLC, and reverse-phase HPLC. Amino-terminal amino acid sequencing revealed that essentially all molecules contained an additional amino-terminal methionine. The specific antiviral activity of EqIFN-beta 1 determined on equine dermal fibroblasts challenged with vesicular stomatitis virus (VSV) was approximately 5 X 10(8) U/mg. Less than 0.001% of this activity was observed in antiviral assays using human (A549), murine (L-M), ovine (SCP), or bovine (MDBK and BT) cells challenged with VSV or encephalomyocarditis virus. A series of monoclonal murine IgG antibodies were developed which neutralize the antiviral activity of EqIFN-beta 1. None of these antibodies nor rabbit antiserum to EqIFN-beta 1 were able to neutralize human IFN-beta; antiserum to human IFN-beta did not neutralize EqIFN-beta 1. Two of the monoclonal antibodies were used to establish a rapid one-step solid-phase enzyme immunoassay for EqIFN-beta 1.
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PMID:Recombinant equine interferon-beta 1: purification and preliminary characterization. 220 Aug 32

We examined the sensitivity of four human germ-cell-tumor cell lines exhibiting different stages of differentiation to human interferons (IFNs) in vitro. The cell lines were derived from two embryonal carcinomas (NEC 8 and NEC 14), a choriocarcinoma (IMa), and a yolk-sac tumor (HUOT). Treatment with poly I:C induced IFN production in IMa and HUOT cells, but not in NEC-8 and NEC-14 cells. In the two embryonal-carcinoma cell lines, the addition of IFN-alpha, IFN-beta, and IFN-gamma did not prevent infection by vesicular stomatitis virus and encephalomyocarditis virus. Also, in these two lines, 2-5A synthetase was not induced by the addition of IFN-alpha. In contrast, both IMa and HUOT showed sensitivity to the antiviral action of IFN-alpha and IFN-beta against the two viruses, and 2-5A synthetase was induced by IFN-alpha. IFNs added at doses of up to 1000 IU/ml had no antiproliferative effect on NEC 8, NEC 14, and HUOT, whereas colony formation by IMa cells was greatly suppressed by all three forms of IFN. These results indicate that the production of and sensitivity to IFN are developmentally regulated and are related to the level of differentiation of human germ-cell stem cells.
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PMID:Sensitivity of human germ-cell-tumor cell lines to human interferons. 243 4

Three cell lines tera I, tera II, and PA1, derived from human teratocarcinomas were tested for their capacity to produce interferon (IFN) and for their sensitivity to both human IFN-alpha and IFN-beta. When treated with Newcastle disease virus or Sendai virus, or a synthetic polyribonucleotide, poly(rI):poly(rC), tera I cells produced no IFN and the 2',5'-oligoadenylate (2-5A) synthetase enzymatic pathway was not activated, although there was an increase in protein kinase. In contrast, tera II and PA1 cells produced IFN and both enzymatic activities were detected. IFN treatment has no effect on the growth of any of the cell lines. Tera I and PA1 cells did not develop resistance to challenge with vesicular stomatitis virus or encephalomyocarditis virus, but the growth of a type-C baboon retrovirus was inhibited. Tera II cells were protected against all three viruses. It appears that human teratocarcinoma cell lines can thus differ greatly in their ability to produce IFN and to respond to it.
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PMID:Interferon inducibility and sensitivity of human teratocarcinoma-derived cell lines. 244 Sep 57

The antiviral action of recombinant human tumor necrosis factor (TNF) was studied using assay systems to determine inhibition of viral cytopathic effect (CPE), as well as suppression of virus growth measured by plaque assays. TNF was cloned and prepared by Asahi Chemical Industry, Japan. Antiviral activity against human herpes simplex virus (HSV) types 1 and 2, cytomegalovirus (CMV), varicella-zoster virus (VZ), vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMC), was demonstrated in human diploid fibroblasts following pretreatment with TNF overnight. The antiviral action was completely neutralized by anti-interferon (IFN)-beta serum, but not by anti-IFN-alpha or -gamma antibodies. This suggested the induction of IFN-beta by TNF. The antiviral action was synergistically enhanced by human IFN-gamma. Several non-human cell lines were tested but 10 of 11 failed to be protected from VSV- and/or EMC-induced CPE following pretreatment by TNF. The anticellular effects of TNF were tested in human and in non-human tumor cell lines. The results indicate that the susceptibility of cells to the two activities of TNF, antiviral and anticellular, was distinct, and that antiviral activity of TNF is more species-specific than its anticellular action.
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PMID:Antiviral effects of recombinant human tumor necrosis factor. 244 53

Tumour necrosis factor (TNF) induces antiviral activity in HEp-2 cells. Virus yield reduction assays with vesicular stomatitis virus as challenging virus demonstrated that the antiviral state was more pronounced in confluent cultures under low serum conditions. A significant enhancement of the antiviral state was obtained by combining TNF with low concentrations of either interferon (IFN)-beta 1 or IFN-gamma. The reduction in virus yield was significantly higher than that expected from summation of the independent antiviral activities of either substance alone, i.e. TNF and IFN acted synergistically as antiviral agents. Synergism of TNF with IFN-beta or IFN-gamma appeared to be mediated by different pathways, since different requirements for pretreatment and different effects on oligo-2',5'-adenylate synthetase (2-5AS) induction were observed. Induction of 2-5AS by TNF could be shown to be an indirect event that was sensitive to an antiserum against natural IFN-beta 1.
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PMID:Antiviral activity of tumour necrosis factor. Synergism with interferons and induction of oligo-2',5'-adenylate synthetase. 246 15

Protein kinase C (PKC) inhibitors: Hidaka's compounds H-7 (10 microM) and H-8 (20 microM), palmitoyl-carnitine (10 microM) and phloretin (50 microM), did not modify the antiviral effect of human natural or recombinant interferon alpha and of natural interferon beta. The tumor promoter 12-o-tetradecanoyl-phorbol-13-acetate (TPA) (200 nM), known as activator of PKC induced an antiviral state when tested on human embryo fibroblasts challenged with the vesicular stomatitis virus. The battery of PKC inhibitors used inhibited the antiviral effect induced by TPA. Palmitoyl-carnitine (10 microM) exerted a toxic effect that was reversed by interferon treatment (2,000 IU/ml interferon alpha). These results suggest that PKC, possibly activated by interferon-receptor interaction, is not essential for inducing the antiviral effect of interferon, but, probably, mediates the antiviral effect of TPA.
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PMID:Protein kinase C and the antiviral effect of human interferon. 248 Jun 87


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