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Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA
Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA
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interferon-γ and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice . Journal of Clinical Investigation 87 739 – 742 . ( doi:10.1172/JCI115055 ) di Cesare E Previti M Russo F Brancatelli S Ingemi MC Scoglio R Mazzù N
Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany
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Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany
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Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany
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Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany
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Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany
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Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany
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Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany
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Introduction Interferon alfa is therapeutically used, e.g. in malignant diseases and chronic viral hepatitis. Recombinant human interferon alfa has proven its antiviral effect in several licensing trials ( McHutchison et al. 1998
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ABSTRACT
The distribution of α-interferon in human placental tissue was investigated by immunocytochemical study of paraffin wax-embedded tissue sections using a sheep α-interferon antiserum. Fifty-eight placentas of gestational ages from 8 to 40 weeks were examined.
α-Interferon was present in the syncytiotrophoblast of the chorionic villi of all placentas and was also in macrophages in 28 cases. The appearances suggest production of interferon in human placental trophoblast and, in view of its diverse biological effects, support the concept of a role for α-interferon in the complex series of events required for successful gestation.
J. Endocr. (1988) 119, 531–534
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present in HT and has a crucial role in the pathogenesis of the disease by secreting inflammatory cytokines such as interferon-γ (IFN-γ; Salgame et al . 1991 , Romagnani 1994 , Carter & Dutton 1996 , Pala et al . 2000 , Mazziotti et al . 2003
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If the knowledge accumulated in the past 4 years on the reproductive role of interferon-α (IFN-α) had been available 20 years ago, then there is no doubt that this molecule would have been designated as a reproductive hormone. Eventually some workers would have expressed surprise that the molecule also exhibited properties of a lymphokine, though it might well have been argued that the findings were the result of contamination in 'pure' preparations of the hormone. But the surprise has been in the opposite direction: a material which is considered as an archetypal lymphokine has been very belatedly identified as a major embryonic signal in several mammalian species. The extent of this 'surprise' may be judged from a recent review in this Journal which described (with admirable clarity and detail) the possible role of lymphokines in endocrinology but made no mention of the fact that endocrinology has just hijacked the most
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ABSTRACT
Sequencing of the 40 N-terminal amino acids of the blastocyst protein responsible for blocking corpus luteum regression in early pregnancy in sheep revealed a 37% homology with human α-interferon; 28% of the remaining amino acid changes were conservative. 125I-Labelled human α-interferon bound to membrane receptors from sheep uteri with an approximate Kd of 4 × 10−11 M; binding was inhibited by unlabelled α-interferon or purified blastocyst antiluteolytic protein. The blastocyst antiluteolytic protein therefore closely resembles the interferon-α family of antiviral proteins.
Pharmacology Research 4, Novo Nordisk A/S, Novo Nordisk Park F6.2.13, DK 2760 Måløv, Denmark
Steno Diabetes Center, Niels Steensensvej 2, DK 2820 Gentofte, Denmark
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Pharmacology Research 4, Novo Nordisk A/S, Novo Nordisk Park F6.2.13, DK 2760 Måløv, Denmark
Steno Diabetes Center, Niels Steensensvej 2, DK 2820 Gentofte, Denmark
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Pharmacology Research 4, Novo Nordisk A/S, Novo Nordisk Park F6.2.13, DK 2760 Måløv, Denmark
Steno Diabetes Center, Niels Steensensvej 2, DK 2820 Gentofte, Denmark
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Pharmacology Research 4, Novo Nordisk A/S, Novo Nordisk Park F6.2.13, DK 2760 Måløv, Denmark
Steno Diabetes Center, Niels Steensensvej 2, DK 2820 Gentofte, Denmark
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Pharmacology Research 4, Novo Nordisk A/S, Novo Nordisk Park F6.2.13, DK 2760 Måløv, Denmark
Steno Diabetes Center, Niels Steensensvej 2, DK 2820 Gentofte, Denmark
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Introduction The proinflammatory cytokines interleukin-1β (IL-1β), interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) are toxic to pancreatic β-cells and have been implicated in the pathogenesis of type 1 diabetes ( Eizirik
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ABSTRACT
The ruminant conceptus secretes proteins during early pregnancy which maintain the corpus luteum. These trophoblast proteins are related to the αII-interferons and prevent luteolysis indirectly by disrupting the secretion of endometrial prostaglandin. Although trophoblast interferons appear to be largely confined to the uterine lumen, it remains possible that they also act peripherally. This report describes in vitro studies which suggest that interferon may influence hormone secretion by the ovary directly. The study employed i) a well defined serum-free culture model in which bovine granulosa cells secrete the luteal hormones progesterone and oxytocin, and ii) serum-free and serum-supplemented cultures of cells from early CL. Dose-response experiments were performed using bovine recombinant α-interferon (brIFN). Progesterone and oxytocin secretions were measured over 4-5 days of culture and DNA content was also determined.
Low concentrations of brIFN (10−15 mol/l to 10−11 mol/l) stimulated progesterone secretion by granulosa cells by up to three fold, without significantly affecting oxytocin concentrations or culture DNA content. Concentrations of 10−10 mol/l to 10−7 mol/l suppressed progesterone secretion in a log dose-related manner (r=0.97) with evidence of toxicity (lower oxytocin concentrations and significantly reduced DNA compared with controls). Progesterone secretion by luteal cells in serum-free culture was stimulated in the presence of 10−15 mol/l brIFN, whilst high concentrations again caused inhibition. The data show that ovarian cells can respond directly to low concentrations of interferon-like proteins. They also demonstrate an inhibition by high doses which may mask the stimulatory effect in this model. The data suggest that the early corpus luteum may be directly influenced by α-interferon. A stimulation of progesterone, but not of oxytocin, secretion from ovarian cells would be consistent with a role for conceptus proteins in maintaining the corpus luteum of pregnancy.
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, Arzt 2001 , Nudi et al . 2005 ). Previous reports showed that interferon-γ (IFNG), a potent immunostimulatory cytokine, also plays a regulatory role in the adenohypophysis. Vankelecom et al . (1990 , 1992 ) described that IFNG inhibits agonist
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ABSTRACT
Ovine endometrial cells were isolated from ovariectomized oestrogen and progesterone-treated ewes and maintained in primary culture. In-vitro treatment with human interferon-α2 (Roferon, Hoffman La Roche) (5, 50 IU/ml) or purified ovine trophoblast protein 1 (oTP-1, 30 ng/ml) significantly attenuated PGF2α (25±17, 29±17, 28±9%±SEM of control [no in-vitro treatment = 100%] respectively, N=4 ewes) and PGE (11±4, 16±4, 16±5% of control) release from the cultured cells. Fluorography of two dimensional polyacrylamide gel electrophoretic analyses of proteins secreted by the cells following 35S-methionine incorporation, revealed that synthesis and secretion of the same "pregnancy-related" proteins was stimulated by both interferon-α2 and oTP-1. Thus, interferon-α2 (which has sequence homology with oTP-1) acts on the ovine endometrium, eliciting similar biological responses to those of oTP-1.
