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Interferon-stimulated Genes (interferon-stimulated + gene)

Distribution by Scientific Domains

Medical Sciences	50%
Chemistry	33%

Selected Abstracts

Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy

ANNALS OF NEUROLOGY, Issue 1 2010
Mohammad Salajegheh MD
Objective We investigated interferon-stimulated gene 15 (ISG15), a poorly understood ubiquitin-like modifier, and its enzymatic pathway in dermatomyositis (DM), an autoimmune disease primarily involving muscle and skin. Methods We generated microarray data measuring transcript abundance for approximately 18,000 genes in each of 113 human muscle biopsy specimens, and studied biopsy specimens and cultured skeletal muscle using immunohistochemistry, immunoblotting proteomics, real-time quantitative polymerase chain reaction, and laser-capture microdissection. Results Transcripts encoding ISG15-conjugation pathway proteins were markedly upregulated in DM with perifascicular atrophy (DM-PFA) muscle (ISG15 339-fold, HERC5 62-fold, and USP18 68-fold) compared with 99 non-DM samples. Combined analysis with publicly available microarray datasets showed that >50-fold ISG15 transcript elevation had 100% sensitivity and specificity for 28 biopsies from adult DM-PFA and juvenile DM patients compared with 199 muscle samples from other muscle diseases. Free ISG15 and ISG15-conjugated proteins were only found on immunoblots from DM-PFA muscle. Cultured human skeletal muscle exposed to type 1 interferons produced similar transcripts and ISG15 protein and conjugates. Laser-capture microdissection followed by proteomic analysis showed deficiency of titin in DM perifascicular atrophic myofibers. Interpretation A large-scale microarray study of muscle samples demonstrated that among a diverse group of muscle diseases DM was uniquely associated with upregulation of the ISG15 conjugation pathway. Exposure of human skeletal muscle cell culture to type 1 interferons produced a molecular picture highly similar to that seen in human DM muscle. Perifascicular atrophic myofibers in DM were deficient in a number of skeletal muscle proteins including titin. ANN NEUROL 2010;67:53,63 [source]

Proteome responses to stable hepatitis B virus transfection and following interferon alpha treatment in human liver cell line HepG2

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2009
Jianghua Wang
Abstract Hepatitis B virus (HBV) infection is a worldwide health problem and may develop to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. To investigate the global proteome responses of liver-derived cells to HBV infection and IFN, treatment, 2-DE and MS-based analysis were performed to compare the proteome changes between HBV stably transfected cell line HepG2.2.15 and its parental cell line HepG2, as well as HepG2.2.15 before and after IFN, treatment (5000,IU/mL for 72,h). Compared to HepG2, 12 of 18 down-regulated and 27 of 32 up-regulated proteins were identified in HepG2.2.15. After IFN, treatment, 6 of 7 down-regulated and 11 of 14 up-regulated proteins were identified. Differentially expressed proteins caused by HBV infection were involved with cytoskeletal matrix, heat shock stress, kinases/signal transduction, protease/proteasome components, etc. Prohibitin showed a dose-dependent up-regulation during IFN, treatment and might play a potent role in anti-HBV activities of IFN, by enhancing the crossbinding p53 expression to achieve the apoptosis of HBV infected liver cells. Down-regulation of interferon-stimulated gene 15 (ISG15) in HepG2.2.15 and recovery by IFN, suggested its relationship with IFN,'s anti-HBV effect. [source]

Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy

The interferon alpha induced protein ISG12 is localized to the nuclear membrane

FEBS JOURNAL, Issue 22 2001
Pia M. Martensen
Interferons exert their biological function mainly through the activation of interferon-stimulated genes (ISGs). ISG12 (originally designated p27) belongs to a family of small, interferon , inducible genes of unknown function. We have determined the 5, end sequence of ISG12 cDNA from the human cell lines HeLa and AMA by RACE. Comparing this sequence to ISG12 sequences in the expressed sequence tag (EST) database revealed the presence of two alternative splice variants of ISG12 in human cells exhibiting the same open reading frame. We have sequenced the promoter region of the ISG12 gene and found ISRE, IRF1/IRF2, and STAT elements correlating to the interferon , inducibility of the gene. Subsequently, we have expressed human ISG12, a 12-kDa hydrophobic protein in the baculovirus expression system and with a C-terminal FLAG-tag in the human cell line 293. Recombinant ISG12 sediments in the nuclear envelope in both cell types. Finally, we have been able to demonstrate the prevalence of the ISG12 gene product in the nuclear envelope of HeLa cells treated with interferon , by immunocytochemical analyses. ISG12 is the first interferon induced protein found localizing to the nuclear envelope. [source]

REVIEW ARTICLE: Effects of Early Conceptus Signals on Circulating Immune Cells: Lessons from Domestic Ruminants

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010
Troy L. Ott
Citation Ott TL, Gifford CA. Effects of early conceptus signals on circulating immune cells: lessons from domestic ruminants. Am J Reprod Immunol 2010 While there are few similarities between mechanisms for extending corpus luteum (CL) function during early pregnancy in ruminants and primates, there is increasing evidence that conceptus-immune crosstalk in ruminants and primates affects the function of circulating immune cells at the very earliest stages of pregnancy. Most notable are changes in immune cell phenotypes with increased numbers of cells exhibiting the T regulatory phenotype and suppression of Th1 cytokines that promote tolerance to paternal alloantigens. Until recently, interferon , produced by the ruminant trophectoderm was thought to act exclusively on the uterine endometrium; however, it is now clear that this unique embryonic interferon escapes the uterus and alters gene expression in the CL and in peripheral blood leukocytes (PBL). In fact, a large number of interferon-stimulated genes are now known to be increased during early pregnancy in PBL. What is not known is how this conceptus-immune system cross-talk affects maternal immune status outside the reproductive tract. It is attractive to hypothesize that some of these effects are designed to counter-balance progesterone-induced immunosuppression so as not to place the dam at a greater risk of infection on top of the tremendous stresses already induced by pregnancy. Furthermore, recent evidence suggests that pregnancy induced changes in peripheral immune cells may aid in orchestrating establishment of pregnancy. Existing evidence points toward a greater convergence of systemic immune responses to early pregnancy signaling between ruminants and primates. [source]

Interferons and viral infections

BIOFACTORS, Issue 1 2009
Volker Fensterl
Abstract Interferons represent a family of cytokines, which is of central importance in the innate immune response to virus infections. All interferons act as secreted ligands of specific cell surface receptors, eliciting the transcription of hundreds of interferon-stimulated genes whose protein products have antiviral activity, as well as antimicrobial, antiproliferative/antitumor, and immunomodulatory effects. Expression of type I and III interferons is induced in virtually all cell types upon recognition of viral molecular patterns, especially nucleic acids, by cytoplasmic and endosomal receptors, whereas type II interferon is induced by cytokines such as IL-12, and its expression is restricted to immune cells such as T cells and NK cells. The effectiveness of the interferon system in counteracting viral infections is reflected by the multitude of inhibitors of interferon induction or interferon action that are encoded by many viruses, preventing their eradication and resulting in the continued coexistence of viruses and vertebrates. The unique biological functions of interferons have led to their therapeutic use in the treatment of diseases such as hepatitis, multiple sclerosis, and certain leukemias. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source]