Journal of interferon research最新文献

Rapid activation of the interferon-gamma signal transduction pathway by inhibitors of tyrosine phosphatases. 酪氨酸磷酸酶抑制剂快速激活干扰素- γ信号转导通路。

Journal of interferon research Pub Date : 1994-12-01 DOI: 10.1089/jir.1994.14.365

P Lamb, J Haslam, L Kessler, H M Seidel, R B Stein, J Rosen

{"title":"Rapid activation of the interferon-gamma signal transduction pathway by inhibitors of tyrosine phosphatases.","authors":"P Lamb, J Haslam, L Kessler, H M Seidel, R B Stein, J Rosen","doi":"10.1089/jir.1994.14.365","DOIUrl":"https://doi.org/10.1089/jir.1994.14.365","url":null,"abstract":"Induction of gene expression by interferon-gamma involves the activation of a latent cytoplasmic transcription factor, p91, by phosphorylation on a single tyrosyl residue. This phosphorylation triggers dimerization, nuclear translocation, and the binding of p91 to interferon-gamma response elements present in the promoters of induced genes. Phosphorylation of p91 requires the activation of two tyrosine kinases, JAK1 and JAK2, that themselves become phosphorylated on tyrosyl residues shortly after interferon-gamma binds to its receptor. The importance of tyrosine phosphorylation in this pathway prompted us to investigate the role of protein tyrosine phosphatases in the regulation of the pathway. We find that in the absence of interferon-gamma, treatment of cells with an inhibitor of tyrosine phosphatases causes a rapid and potent activation of the components of the interferon-gamma signal transduction pathway and induces an interferon-gamma-responsive gene. This suggests that tyrosine phosphatases act both to repress the interferon-gamma signal transduction pathway in the absence of interferon-gamma and to downregulate the pathway after interferon-gamma induction.","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 6","pages":"365-73"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18895559","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}

引用次数: 22

Interferon-stimulated response element and NF kappa B sites cooperate to regulate double-stranded RNA-induced transcription of the IP-10 gene. 干扰素刺激反应元件和NF κ B位点共同调控双链rna诱导的IP-10基因转录。

Journal of interferon research Pub Date : 1994-12-01 DOI: 10.1089/jir.1994.14.357

C Wu, Y Ohmori, S Bandyopadhyay, G Sen, T Hamilton

{"title":"Interferon-stimulated response element and NF kappa B sites cooperate to regulate double-stranded RNA-induced transcription of the IP-10 gene.","authors":"C Wu, Y Ohmori, S Bandyopadhyay, G Sen, T Hamilton","doi":"10.1089/jir.1994.14.357","DOIUrl":"https://doi.org/10.1089/jir.1994.14.357","url":null,"abstract":"To understand the mechanisms involved in dsRNA-induced gene expression, we analyzed the poly(I/C)-induced transcription of the IFN-inducible chemokine gene IP-10 using the GRE cell line in which type I IFN genes have been deleted. Accumulation of IP-10 mRNA in GRE cells was more strongly stimulated by treatment with dsRNA than by IFN-alpha or IFN-gamma and was independent of protein synthesis. This same pattern of response was produced when GRE cells were transiently transfected with a plasmid containing 243 bases of sequence from the promoter of the murine IP-10 gene linked to the chloramphenicol acetyltransferase reporter gene. Deletion- and site-specific mutagenesis of the 243 base pair fragment indicated that an ISRE located between residues -204 and -228 was a primary target site for the action of dsRNA on this promoter. This was confirmed by results showing that two copies of this ISRE tandemly arrayed in front of the thymidine kinase promoter were able to mediate reporter gene transcription in dsRNA-stimulated cells. At least one of the two NF kappa B binding sites present in the 243 base pair IP-10 promoter is also necessary for response to dsRNA; mutation of both sites eliminates promoter activity. Thus the ISRE and one NF kappa B site cooperate to produce transcriptional response to dsRNA.","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 6","pages":"357-63"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18895558","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}

引用次数: 54

Defective transport of herpes simplex virus glycoprotein in interferon-treated cells: role of intracellular pH. 干扰素处理细胞中单纯疱疹病毒糖蛋白运输缺陷:细胞内pH值的作用。

Journal of interferon research Pub Date : 1994-12-01 DOI: 10.1089/jir.1994.14.319

R K Maheshwari, G S Sidhu, A K Singh, S S Sivaram, P R Kinchington, J Hay, R M Friedman

{"title":"Defective transport of herpes simplex virus glycoprotein in interferon-treated cells: role of intracellular pH.","authors":"R K Maheshwari, G S Sidhu, A K Singh, S S Sivaram, P R Kinchington, J Hay, R M Friedman","doi":"10.1089/jir.1994.14.319","DOIUrl":"https://doi.org/10.1089/jir.1994.14.319","url":null,"abstract":"We have investigated the mechanism(s) of interferon (IFN)-induced inhibition of assembly steps of herpes simplex virus (HSV-1) in mouse LB cells. Data showed that physiological doses of mouse IFN-beta (10-100 IU/ml) significantly inhibited the infectivity (5- to 100-fold) of HSV-1; however, viral protein synthesis was marginally inhibited (2- to 5-fold). Immunofluorescence studies showed that most of the HSV-1gD glycoprotein accumulated intracellularly in IFN-treated LB and LMtk- cells transfected with gD cDNA, as compared to untreated controls, where most of the gD was localized on the plasma membrane. Double-immunofluorescence studies demonstrated that rhodamine-labeled wheat germ agglutinin (WGA) was co-localized with gD protein, suggesting the block was in the transport from the trans-Golgi to the plasma membrane. IFN treatment of LB and LMtk- cells raised the intracellular pH as measured by DAMP distribution and SNARF-1 using laser spectroscopy; this could play an important role in the inhibition of transport of HSV-1gD.","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 6","pages":"319-24"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18897618","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}

引用次数: 11

Interferon-alpha-induced biologic modifications in patients with chronic myelogenous leukemia. 干扰素-α诱导的慢性骨髓性白血病患者的生物学改变。

Journal of interferon research Pub Date : 1994-12-01 DOI: 10.1089/jir.1994.14.349

A M Liberati, M A Horisberger, P Garofani, V De Angelis, A Ferrajoli, F Di Clemente, P Caricchi, D Adiuto, L Fedeli, B Palumbo

{"title":"Interferon-alpha-induced biologic modifications in patients with chronic myelogenous leukemia.","authors":"A M Liberati, M A Horisberger, P Garofani, V De Angelis, A Ferrajoli, F Di Clemente, P Caricchi, D Adiuto, L Fedeli, B Palumbo","doi":"10.1089/jir.1994.14.349","DOIUrl":"10.1089/jir.1994.14.349","url":null,"abstract":"Serum neopterin (Np), beta 2-microglobulin (beta 2-M), and 2',5'-adenylate (2',5'A) levels and intracellular 2',5'A and human Mx (Hu-Mx) protein synthesis were measured in 20-24 chronic myeloid leukemia patients before and during 1 year of IFN-alpha treatment and in a further 8-9 patients before and at the end of the first and second treatment weeks only. Univariate analysis showed that IFN-alpha increased Np and 2',5'A serum levels and intracellular concentrations of 2',5'A and Hu-Mx significantly from the end of the first week to month 12 of therapy. The biologic marker profiles were similar in cytogenetic responders and nonresponders, as well as in patients treated with IFN-alpha early (< 12 months from diagnosis) or late (after > 12 months standard chemotherapy). Further, there were no differences in the short-term (first 14 days) or long-term (during 12 month therapy) induction of the biologic markers irrespective of whether IFN-alpha 2a or IFN-alpha 2b was given. Because multivariate analysis revealed no significant interactions between cytogenetic response, time to treatment, and type of IFN-alpha used, increments in intracellular 2',5'A and Hu-Mx protein were similar at all study times for all factor combinations tested. Np levels varied significantly only during the first 14 therapy days; changes in serum 2',5'A were never statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 6","pages":"349-55"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18895557","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}

引用次数: 8

Human indoleamine 2,3-dioxygenase inhibits Toxoplasma gondii growth in fibroblast cells. 人吲哚胺2,3-双加氧酶抑制弓形虫成纤维细胞生长。

Journal of interferon research Pub Date : 1994-12-01 DOI: 10.1089/jir.1994.14.313

W Dai, H Pan, O Kwok, J P Dubey

{"title":"Human indoleamine 2,3-dioxygenase inhibits Toxoplasma gondii growth in fibroblast cells.","authors":"W Dai, H Pan, O Kwok, J P Dubey","doi":"10.1089/jir.1994.14.313","DOIUrl":"https://doi.org/10.1089/jir.1994.14.313","url":null,"abstract":"Interferon-gamma (IFN-gamma) is known to inhibit the growth of Toxoplasma gondii both in vivo and in vitro. The IFN-gamma induced anti-toxoplasma activity in human cells is strongly correlated with the degradation of the essential amino acid L-tryptophan in vitro. Destruction of L-tryptophan is due to an increased activity of indoleamine 2,3-dioxygenase (IDO), which is transcriptionally activated by IFN-gamma. To determine if indoleamine 2,3-dioxygenase alone is sufficient to block the T. gondii growth, we transfected human fibroblast cells with an IDO cDNA expression plasmid using a metallothionein-inducible promoter. We showed that IDO mRNA and its enzymatic activity are inducible in fibroblast cells transfected with right-orientation IDO cDNA upon addition of CdCl2 to culture medium. The elevated IDO enzyme activity is strongly correlated with an inhibition of T. gondii growth. No IDO mRNA nor enzyme activity is induced by CdCl2 in reverse orientation transfected cells, and no adverse effects were observed on T. gondii growth in cells transfected with the reverse IDO-construct or in control parent cells with or without supplementation of CdCl2. Our observations along with the recent report by Habara-Ohkubo et al. (Infect. Immun. 61, 1810-1813, 1993) suggest that IFN-gamma-induced antitoxoplasma activity is due at least in part to the activation of IDO gene.","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 6","pages":"313-7"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18897617","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}

引用次数: 55

Modulation of peripheral leukocyte counts and bone marrow function in mice by oral administration of interleukin-2. 口服白介素-2对小鼠外周血白细胞计数和骨髓功能的调节。

Journal of interferon research Pub Date : 1994-12-01 DOI: 10.1089/jir.1994.14.343

S Koren, W R Fleischmann

引用次数: 5

IDO mutants cross resistant to type I interferon retain p91-dependent gene induction. 对I型干扰素产生交叉抗性的IDO突变体保留了p91依赖性基因诱导。

Journal of interferon research Pub Date : 1994-12-01 DOI: 10.1089/jir.1994.14.333

S B Klein, A Yeivin, G Becker, M W Taylor

{"title":"IDO mutants cross resistant to type I interferon retain p91-dependent gene induction.","authors":"S B Klein, A Yeivin, G Becker, M W Taylor","doi":"10.1089/jir.1994.14.333","DOIUrl":"https://doi.org/10.1089/jir.1994.14.333","url":null,"abstract":"Genetic analyses of mutants have yielded valuable information about p91-associated interferon signal transduction. It was thus discovered that p91 is an essential protein for the induction of both type I and type II interferons. We previously reported the development of ME180 mutants resistant to interferon-gamma because of a signaling defect resulting in the loss of IDO induction. IDO does not respond to type I interferon despite an ISRE-like sequence upstream of the coding region. However, the IDO mutants were found to be cross-resistant to the growth-inhibitory effects of type I interferon. We therefore examined the effects of both types of interferon on interferon-stimulated gene mRNA accumulation and examined alterations in cellular protein introduced by the mutation. The induction of the p91-responsive gene 6-16 was not altered in either of the mutants, and the early-induced gene IRF1 exhibited differences only in the kinetics of mRNA accumulation. The later induced gene, p68, also exhibited different kinetics, possibly reflecting the changes in IRF1. Immunoprecipitated p91 exhibited normal, interferon-induced phosphorylation in both mutants. Two-dimensional gel electrophoresis revealed that the mutant cells contained 20 peptides with altered biochemistry. These results suggest that IDO induction is controlled by a distinct set of proteins not directly correlated with p91 activation.","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 6","pages":"333-41"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18897620","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}

引用次数: 2

Interferon-alpha 2 produced by normal human leukocytes is predominantly interferon-alpha 2b. 正常人白细胞产生的干扰素- α 2主要是干扰素- α 2b。

Journal of interferon research Pub Date : 1994-12-01 DOI: 10.1089/jir.1994.14.325

M Dipaola, T Smith, K Ferencz-Biro, M J Liao, D Testa

{"title":"Interferon-alpha 2 produced by normal human leukocytes is predominantly interferon-alpha 2b.","authors":"M Dipaola, T Smith, K Ferencz-Biro, M J Liao, D Testa","doi":"10.1089/jir.1994.14.325","DOIUrl":"https://doi.org/10.1089/jir.1994.14.325","url":null,"abstract":"Peripheral blood leukocytes, isolated from the buffy coats of greater than 10,700 normal healthy donors, were induced with Sendai virus to produce biologically active interferon alpha (IFN-alpha). The IFN-alpha was purified to near homogeneity by immunoaffinity chromatography, followed by size-exclusion chromatography. The resultant product, IFN-alpha n3, is reproducibly > or = 98% pure (to be reported elsewhere). The different IFN-alpha proteins in IFN-alpha n3 were separated by reverse-phase high performance liquid chromatography (RP-HPLC) and the identity of the IFN-alpha 2 isolated by HPLC was determined by amino-terminal sequencing. IFN-alpha 2 was found to migrate as two closely eluting peaks on RP-HPLC, and they have been designated as peaks 1.1 and 1.2. Distinction among the three possible variants of IFN-alpha 2, i.e., IFN-alpha 2a, IFN-alpha 2b, and IFN-alpha 2c, was determined by amino-terminal sequencing of the first 35 amino acids in peaks 1.1 and 1.2. Protein sequence data showed that the discriminating amino acids found at positions 23 and 34 are Arg and His, respectively. The presence of Arg and not Lys at amino acid position 23 and His at amino acid position 34 argues that IFN-alpha 2b is the major component in the Sendai virus-induced leukocyte IFN-alpha 2 and that IFN-alpha 2a is not present. These findings were verified by subjecting RP-HPLC peaks 1.1 and 1.2 to CNBr cleavage, followed by separation of the fragments by RP-HPLC and sequencing.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":16268,"journal":{"name":"Journal of interferon research","volume":"14 6","pages":"325-32"},"PeriodicalIF":0.0,"publicationDate":"1994-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1089/jir.1994.14.325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18897619","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}

引用次数: 14

Antibody to the human interferon-alpha receptor reduces the loss of CD4+ T cells in macaques infected with the simian immunodeficiency virus, SIVmac. 人干扰素- α受体抗体可减少猴免疫缺陷病毒(SIVmac)感染的猕猴体内CD4+ T细胞的损失。

Journal of interferon research Pub Date : 1994-10-01 DOI: 10.1089/jir.1994.14.287

M G Tovey, P Lebon, P Eid, F Meyer, B Hurtrel, I Gresser, A Venet, M Girard, A M Aubertin

引用次数: 1

Pentoxifylline inhibits tumor necrosis factor production in septic shock. 己酮茶碱抑制感染性休克中肿瘤坏死因子的产生。

Journal of interferon research Pub Date : 1994-10-01 DOI: 10.1089/jir.1994.14.293

G M Matuschak, K E Lamprech, A J Lechner

引用次数: 8