Inhibition of ornithine decarboxylase in human fibroblast cells by type I and type II interferons

Sekar, Vaithilingam; Atmar, Valerie J.; Joshi, Arati R.; Krim, Mathilde; Kuehn, Glenn D.

doi:10.1016/0006-291x(83)90652-6

Cited by 38 publications

(9 citation statements)

References 11 publications

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“…Inhibition of serum-stimulated increases in ODC activity by IFN has been reported in 3T3 cells (Sreevalson et al 19791, murine erythroleukemia cells (Gazitt, 1981), and human fibroblasts (Sekar et al, 1983). Because polyamines are required for the differentiation of murine erythroleukemia cells (Gazitt and Friend, 1980), 3T3 adipocytes (Bethell and Pegg, 1981;Erwin et al, 19841, and L6 myoblasts (Erwin et al, 1983;Ewton et al, 19841, and because differentiation of each cell type is inhibited by IFN, it was reasonable to speculate that IFN inhibits myogenesis by inactivating ODC, thereby depleting polyamine levels required for differentiation.…”

Section: Discussionmentioning

confidence: 91%

Interferon‐mediated inhibition of differentiation in a murine myoblast cell line

Multhauf

Lough

1986

Journal Cellular Physiology

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The effects of highly purified (greater than 5 X 10(7) IU/mg) murine beta-interferon (IFN) on a mouse myoblast line (MM14DZ) have been investigated to confirm and extend the previous observation that partially purified chicken interferon inhibits differentiation of cultured avian myoblasts (Lough et al., Biochem Biophys Res Commun 109:92, 1982). Cultures treated with 20-2,000 lU IFN/ml medium for 5 days exhibited dose-dependent 1) inhibition of differentiation, as indicated by reduced myotube formation and creatine kinase (CK) activity and 2) increases in DNA content, suggesting that the inhibitory effect was accompanied by continued proliferation of myoblasts. Mock-IFN had no such effects. Based on findings in other systems that IFN inhibits activity of ornithine decarboxylase (ODC), the polyamine products of which are required for myogenesis, the hypothesis that inhibition of differentiation was mediated by an effect of IFN on polyamine metabolism was tested. However, observations that 1) IFN-treated myoblasts retained control levels of ODC activity and 2) exogenous polyamines did not prevent IFN-inhibition did not indicate such a mechanism of action. On the other hand, treatment of control cultures with polyamines alone resulted in potentiation of myogenesis as revealed by precocious myotube formation and a marked increase in CK activity.

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Section: Discussionmentioning

confidence: 91%

Interferon‐mediated inhibition of differentiation in a murine myoblast cell line

Multhauf

Lough

1986

Journal Cellular Physiology

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“…Although the 2'-5'-OAS/RNaseL system is involved in inhibiting viral protein synthesis, there is growing evidence that suggests it also inhibits cellular protein synthesis, leading to inhibition of cell division [6]. In addition, several other IFNinduced effects, including increased cell rigidity [95], depletion of essential metabolites [96,97], and suppression of oncogenes [98], could be involved in the antiproliferative capacity of IFN.…”

Section: Mechanisms Of Antiviral Responsementioning

confidence: 99%

Interferon: Cellular Executioner or White Knight?

Maher¹,

Romero-Weaver²,

Scarzello³

et al. 2007

CMC

147

131

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Interferons (IFNs) are a family of pleiotropic cytokines that typically exhibit antiviral, antiproliferative, antitumor, and immunomodulatory properties. While their complex mechanisms of action remain unclear, IFNs are used clinically in the treatment of viral infections, such as hepatitis B and hepatitis C, and remain the primary treatment for a limited number of malignancies, such as melanoma, hairy cell leukemia, and non-Hodgkin's lymphoma and in autoimmune diseases such as multiple sclerosis. IFNs not only regulate somatic cell growth and division but also influence cell survival through the modulation of apoptosis. Paradoxically, IFNs are described to be both pro- and anti-apoptotic in nature. The biological effects of IFNs are primarily mediated via activation of the JAK/STAT pathway, formation of the ISGF3 and STAT1:STAT1 protein complexes, and the subsequent induction of IFN-stimulated genes. However, the activation of JAK/STAT-independent signal transduction pathways also contribute to IFN-mediated responses. To further demonstrate the complexity of the downstream events following stimulation, oligonucleotide microarray studies have shown that in excess of 300 genes are induced following treatment with IFN, some of which are crucial to the induction of apoptosis and cell growth control. In this review we describe the recent advances made in elucidating the various signaling pathways that are activated by IFNs and how these diverse signals contribute to the regulation of cell growth and apoptosis and inhibition of viral replication. Furthermore, we highlight the role of specific signaling molecules and the function(s) of particular IFN-stimulated genes that have been implicated in determining cell fate in response to IFN, as well as the clinical experience of IFN immunotherapy.

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“…Downregulation of expression of speci®c genes by IFNs may also negatively regulate growth (Pestka et al, 1987). This possibility is suggested by several lines of evidence: (1) IFNs down-regulate expression of growth factor receptors thereby antagonizing the growth promoting eects of speci®c growth factors (Zoon et al, 1986); (2) IFNs inhibit the activity of ornithine decarboxylase which is a rate-limiting enzyme in the biosynthesis of polyamines (Sreevalsan et al, 1980;Sekar et al, 1983); and (3) IFNs inhibit genes involved in cell growth (Harel-Bellam et al, 1988;Chatterjee and Savarese, 1992). These results suggest that multiple mechanisms may underlie the ability of IFNs to inhibit cell growth.…”

Section: Introductionmentioning

confidence: 99%

Suppression of human ribosomal protein L23A expression during cell growth inhibition by interferon-β

et al. 1997

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Interferons inhibit cell growth in normal and tumorderived cells. The molecular basis of interferons antiproliferative activity remains to be de®ned. Using subtraction hybridization, a human melanoma dierentiation associated gene, mda-20, has been identi®ed that is down-regulated by treatment with interferon. Sequence analysis indicates that mda-20 is human ribosomal protein L23a (rp L23a). The mRNA levels of rp L23a and growth are diminished in a variety of human tumor cell lines following treatment with human ®broblast interferon, interferon-b (IFN-b). Expression of rp L23a is also reduced in human melanoma cells treated with human leukocyte (IFN-a) and immune (IFN-g) interferons, but not by growth inhibition resulting from serum starvation. These ®ndings suggest that growth suppression alone is not sucient to reduce rp L23a expression. Instead, reduced rp L23a mRNA results from biochemical changes mediated by interferons. Ectopic expression of an antisense rp L23a sequence in human HeLa cervical carcinoma cells results in a reduction in colony formation indicating a direct antiproliferative eect by inhibiting rp L23a expression. The mechanism underlying inhibition in rp L23a expression in IFN-b-treated cells may involve antisense rp L23a RNA. These results suggest that rp L23a may be one of the target molecules involved in mediating growth inhibition by interferon.

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Inhibition of ornithine decarboxylase in human fibroblast cells by type I and type II interferons

Cited by 38 publications

References 11 publications

Interferon‐mediated inhibition of differentiation in a murine myoblast cell line

Interferon‐mediated inhibition of differentiation in a murine myoblast cell line

Interferon: Cellular Executioner or White Knight?

Suppression of human ribosomal protein L23A expression during cell growth inhibition by interferon-β

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