{"title":"Reversal of interferon-gamma-resistant phenotype by poly(I:C): possible involvement of ISGF2 (IRF1) in interferon-gamma-mediated induction of the IDO gene.","authors":"O N Ozes, M W Taylor","doi":"10.1089/jir.1994.14.25","DOIUrl":"https://doi.org/10.1089/jir.1994.14.25","url":null,"abstract":"<p><p>Indoleamine 2,3-dioxygenase (IDO) is induced in many cell lines by interferon-gamma (IFN-gamma) treatment. IDO mRNA increases rapidly from 4 h after IFN-gamma treatment to at least 24 h after treatment in ME180 cells. The IFN-gamma-resistant mutant of ME180, IR3B6B, expresses only one-sixth the amount of IDO message after IFN-gamma treatment and very low levels of IDO. However, pretreatment of these mutants with poly(I:C) restores normal levels of IDO mRNAs and IDO activity. Since IRF1 mRNA induction is also low in IR3B6B cells after IFN-gamma treatment, we examined whether there was any relationship between IRF1 induction and IDO induction by IFN-gamma. The steady-state level of IRF1 mRNA was elevated by treating IR3B6B cells with poly(I:C) and IFN-gamma. Poly(I:C)-mediated reversal of IFN-gamma-resistant phenotype and induction of IDO and IRF1 messages are inhibited by 2-aminopurine. Transient transfection of IRF1 cDNA in ME180 cells resulted in activation of IDO transcription. Nuclear extracts prepared from IFN-gamma-treated ME180 and IR3B6B cells affected differently the mobility of a 80-bp DNA fragment of the 5' regulatory region of IDO gene. Pretreatment of IR3B6B cells with poly(I:C) and addition of IFN-gamma resulted in increased DNA binding of nuclear proteins to the DNA. Pre- and post-treatment of nuclear extract of IFN-gamma-treated ME180 cells with anti-IRF1 antibody resulted in a super shift in mobility of the probe with the abolishment of normal gel-shift pattern.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 1","pages":"25-32"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19025698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibitory effect of interferon-alpha on respiratory burst and glucose metabolism in phagocytic cells.","authors":"M Conde, J Andrade, F J Bedoya, F Sobrino","doi":"10.1089/jir.1994.14.11","DOIUrl":"https://doi.org/10.1089/jir.1994.14.11","url":null,"abstract":"<p><p>Anion superoxide (O2-) production and glucose metabolism was studied in murine macrophages following in vivo or in vitro treatment with human recombinant interferon-alpha 2b (IFN-alpha 2b). The PMA-dependent O2- production was inhibited by IFN-alpha 2b in a concentration- and time-dependent manner. NO2- production by macrophages in culture was slightly inhibited (about 16%) at 30 nM IFN-alpha and a clear decrease (35%) was obtained with 150 nM IFN-alpha. Low doses (0.3 and 3 nM IFN-alpha) had no effect. Also, IFN-alpha 2b inhibited lactate release and 3H2O production from [2-3H] and [3-3H]glucose in macrophages isolated after in vivo treatment for 24 h. The data support an inhibitory role of IFN-alpha in the metabolic activation of macrophages and suggest a putative mechanism for the inhibition of some macrophage functions as previously reported.</p>","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 1","pages":"11-6"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19025696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T A Bhuiya, M Shodell, P A Fitzgerald-Bocarsly, D Murasko, K Shah, D Drake, F P Siegal
{"title":"Interferon-alpha generation in mice responding to challenge with UV-inactivated herpes simplex virus.","authors":"T A Bhuiya, M Shodell, P A Fitzgerald-Bocarsly, D Murasko, K Shah, D Drake, F P Siegal","doi":"10.1089/jir.1994.14.17","DOIUrl":"https://doi.org/10.1089/jir.1994.14.17","url":null,"abstract":"<p><p>In humans with advanced human immunodeficiency virus (HIV) infection, an interferon-alpha (IFN-alpha) response by a specialized blood mononuclear cell to herpes simplex virus (HSV) in vitro is associated with resistance to opportunistic infections. A cell type of unknown lineage, designated the natural IFN-producing cell (NIPC), has been identified preliminarily as the source of these IFNs and may have a role in other host defense functions. Earlier studies suggested the existence of analogous HSV-responsive cell populations in mice. The role specifically of IFN-alpha in the murine system, however, has not been characterized. Using IFN bioassay and neutralization with antisera against Type I IFNs and IFN-beta, we have defined the types and sources of IFNs produced by mice in response to in vivo and in vitro challenge with UV-inactivated HSV. After intraperitoneal inoculation with HSV, BALB/c and C57Bl/6 strains produced characteristically different levels of serum IFNs that appeared principally to be IFN-alpha. The response of mononuclear cells from these mice differed from that of the intact mouse. Isolated cells from bone marrow and spleen released detectable IFNs much later than did whole animals, and the IFNs produced by marrow, spleen, and peritoneal cells were usually neutralized by the anti-IFN-beta. Only bone marrow cells produced detectable amounts of IFN-alpha. Both intact mice and their cells became refractory to restimulation with similar kinetics.</p>","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 1","pages":"17-24"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19025697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Three-dimensional model of a human interferon-alpha consensus sequence.","authors":"A P Korn, D R Rose, E N Fish","doi":"10.1089/jir.1994.14.1","DOIUrl":"https://doi.org/10.1089/jir.1994.14.1","url":null,"abstract":"<p><p>A computer-built, three-dimensional, atomic-level model for human interferon-alpha (IFN-alpha) was constructed. This model was prepared using the primary amino acid sequence of consensus IFN-alpha (IFN-alpha Con1) and the alpha-carbon Cartesian coordinates of murine IFN-beta as a homolog guide to the model building. In agreement with an earlier report from this laboratory, the two domains 29-35 and 123-140 are in close spatial proximity in this model, and may constitute a receptor recognition domain, whereas the region bounded by residues 78-95 is somewhat removed from this region on the molecule and may constitute an alternative active site. Extrapolating from the model, we propose that, of the stretch 123-140, the residues that are exposed are 123, 125, 126, 128-130, and 132-139; and of the stretch 29-35, all are accessible. Additionally, we propose that there may be sufficient complexity in the Type 1 IFN receptor to account for the differential sensitivities between IFN-alpha s and IFN-beta that may be associated with residue differences in the region 78-95, specifically at residues 84, 86, and 87. This model conforms with experimental data that identify specific amino acid residues in human IFN-alpha that either do, or do not, affect the active conformation and biological activities of the molecule.</p>","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18524748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Suppression of mitochondrial mRNA levels and mitochondrial function in cells responding to the anticellular action of interferon.","authors":"J Lou, S L Anderson, L Xing, B Y Rubin","doi":"10.1089/jir.1994.14.33","DOIUrl":"https://doi.org/10.1089/jir.1994.14.33","url":null,"abstract":"<p><p>A lambda cDNA library prepared from polyadenylated RNA isolated from Daudi cells was differentially screened to isolate cDNAs that recognize mRNA whose levels are reduced following interferon (IFN) treatment. Southern blot and DNA sequence analysis of 20 cDNA clones that were isolated revealed that they represented mitochondrially encoded mRNAs for the following proteins: cytochrome c oxidase subunits II and III, ATPase 6, cytochrome b, and subunit 1 of the NADH dehydrogenase. Northern blot analysis employing these cDNAs and oligonucleotides generated to the remaining mitochondrially encoded mRNAs demonstrated that IFN-alpha treatment of Daudi cells mediates a time-dependent suppression of the level of all of the mitochondrially encoded mRNAs. Study of this IFN-mediated effect reveals that: (i) the suppression of the level of these mRNAs is dependent on protein synthesis, (ii) it can be observed to occur prior to any detectable effect on thymidine incorporation, (iii) the degree of suppression correlates with the sensitivity of the cells to the anticellular action of IFN, and (iv) the suppression of the level of these RNAs appears to result from an effect on the level of transcription rather than on the stability of these mRNAs. A study of the level of cellular respiration in IFN-treated Daudi cells reveals a clear suppression 3 h following IFN treatment.</p>","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 1","pages":"33-40"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18527039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P Wang, L Izotova, T M Mariano, R J Donnelly, S Pestka
{"title":"Construction and activity of phosphorylatable human interferon-alpha B2 and interferon-alpha A/D.","authors":"P Wang, L Izotova, T M Mariano, R J Donnelly, S Pestka","doi":"10.1089/jir.1994.14.41","DOIUrl":"https://doi.org/10.1089/jir.1994.14.41","url":null,"abstract":"<p><p>The polymerase chain reaction (PCR) was used to introduce a phosphorylation site into human interferon-alpha B2 (Hu-IFN-alpha B2) and the chimeric human interferon-alpha A/D (Hu-IFN-alpha A/D). The phosphorylation sites were created by adding an amino acid consensus sequence for phosphorylation by the cAMP-dependent protein kinase to the carboxyl termini of the IFNs. The resultant modified IFNs (Hu-IFN-alpha B2-P and Hu-IFN-alpha A/D-P) were expressed in Escherichia coli and purified. The purified proteins exhibited antiviral activities similar to that of unmodified Hu-IFN-alpha B2 and Hu-IFN-alpha A/D. The Hu-IFN-alpha B2-P and Hu-IFN-alpha A/D-P can be phosphorylated by the catalytic subunit of the cAMP-dependent protein kinase and [gamma-32P]ATP with retention of biological activities. The introduction of phosphorylation sites into Hu-IFN-alpha B2 and Hu-IFN-alpha A/D provides new reagents for studies of receptor binding, pharmacokinetics, and other studies where labeled IFNs are useful.</p>","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 1","pages":"41-6"},"PeriodicalIF":0.0,"publicationDate":"1994-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.41","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19025699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R E Curiel, M H Miller, R Ishikawa, D C Thomas, N J Bigley
{"title":"Does the gender difference in interferon production seen in picornavirus-infected spleen cell cultures from ICR Swiss mice have any in vivo significance?","authors":"R E Curiel, M H Miller, R Ishikawa, D C Thomas, N J Bigley","doi":"10.1089/jir.1993.13.387","DOIUrl":"https://doi.org/10.1089/jir.1993.13.387","url":null,"abstract":"<p><p>Splenocyte cultures from female ICR Swiss mice produced greater interferon (IFN) levels, particularly IFN-gamma, than did cultures from males by 12 h post-infection (pi) with the D variant of encephalomyocarditis virus (EMCV-D). This early IFN-gamma is produced by natural killer (NK)-like cells and is dependent on plastic adherent cells and IFN-alpha/beta. In this study, we evaluated the significance of this observation on the innate resistance of ICR Swiss females to EMCV-D-mediated disease. Treatment of females with rabbit anti-mouse IFN-alpha/beta serum rendered them susceptible to the diabetogenicity of EMCV-D. Although sera from both sexes of ICR Swiss mice exhibited peak IFN levels day 3 pi, IFN-gamma was present in the sera of males at only 1 day pi and in the sera of females at days 1-3 pi. Females cleared virus from the circulation by day 2 pi, 1 day earlier than did males. Flow cytometric evaluations of lymphoid cell phenotypes in spleens and pancreata of infected mice revealed that percentages of L3T4+ cells were significantly decreased only in spleens from males at day 1 pi and were diminished along with Ly2+ cells in pancreata of males at 7 days pi, suggesting that T-cell responses were impaired in virus-infected males.</p>","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"13 6","pages":"387-95"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1993.13.387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18520552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nomenclature of the human interferon genes.","authors":"M O Diaz, S Bohlander, G Allen","doi":"10.1089/jir.1993.13.443","DOIUrl":"https://doi.org/10.1089/jir.1993.13.443","url":null,"abstract":"","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"13 6","pages":"443"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1993.13.443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19142877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"U937 cells can utilize plasminogen activator to regulate human interferon-gamma.","authors":"M J Parmely, K E Sterner, A Gale, W W Zhou","doi":"10.1089/jir.1993.13.397","DOIUrl":"https://doi.org/10.1089/jir.1993.13.397","url":null,"abstract":"<p><p>Urokinase-type plasminogen activator (uPA) converts the proenzyme plasminogen to plasmin and thereby contributes to processes like cell migration, tissue remodeling, and cytokine processing. We report here that uPA produced by the human U937 promonocytic cell line also initiated the inactivation of recombinant interferon-gamma (rIFN-gamma) by plasmin-mediated proteolysis. When cultured serum-free with plasminogen, U937 promonocytic cells generated measurable levels of plasmin activity and destroyed the antiviral activity of exogenously added rIFN-gamma. This effect was not seen in the absence of plasminogen, was prevented by inhibitors of uPA and plasmin, and was accompanied by changes in the electrophoretic mobility of rIFN-gamma on polyacrylamide gels, consistent with limited proteolysis of the lymphokine. Culturing U937 cells or blood monocytes for 48 h led to an elevated expression of their surface uPA and an increase in their capacity to produce plasmin and inactivate rIFN-gamma. The ability of rIFN-gamma to induce Fc receptors on U937 cells could also be prevented by providing the cells with a source of exogenous plasminogen, indicating that U937 cells could control their own activation in vitro through the action of uPA. The results of these studies support the conclusion that mononuclear phagocytes have the capacity to use uPA to regulate cytokine activity in vitro.</p>","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"13 6","pages":"397-406"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1993.13.397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19141662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M A Costas, D Mella, M Criscuolo, A Díaz, S Finkielman, V E Nahmod, E Arzt
{"title":"Superinduction of mitogen-stimulated interferon-gamma production and other lymphokines by Sendai virus.","authors":"M A Costas, D Mella, M Criscuolo, A Díaz, S Finkielman, V E Nahmod, E Arzt","doi":"10.1089/jir.1993.13.407","DOIUrl":"https://doi.org/10.1089/jir.1993.13.407","url":null,"abstract":"<p><p>We observed that Sendai virus preinduction of peripheral blood mononuclear cells and subsequent mitogenic stimulation resulted in: (i) Superproduction of interferon-gamma, (IFN-gamma) (ii) an increase in interleukin-2 (IL-2) synthesis that correlates with DNA synthesis when stimulated with phytohemagglutinin (PHA) or pokeweed mitogen (PWM) after treatment with the Sendai virus, while stimulation with Protein A from Staphylococcus aureus was not affected, and (iii) enhanced tumor necrosis factor-alpha (TNF-alpha) production in response to bacterial lipopolysaccharide (LPS). Treatment of monocyte cultures with LPS and cycloheximide or actinomycin-D inhibited the superinduction phenomenon. When cycloheximide was added at the viral induction time, the inhibition of TNF-alpha superproduction and DNA synthesis was still observed. These results suggest that Sendai virus lymphocyte superinduction is specific for a particular stimulatory pathway, not dependent on mRNA accumulation, and probably mediated by induction of an activating protein.</p>","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"13 6","pages":"407-12"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1993.13.407","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19141663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}