Oligodendrocytes exhibit selective expression of suppressor of cytokine signaling genes and signal transducer and activator of transcription 1 independent inhibition of interferon-gamma-induced toxicity in response to leukemia inhibitory factor

Ben Emery, H. Butzkueven, C. Snell, M. Binder, T. J. Kilpatrick

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Multiple sclerosis is an autoimmune disease of the CNS that results in the death of oligodendrocytes, the myelinating cells of the CNS. Previous studies have indicated that the cytokine leukemia inhibitory factor prevents the cytotoxic effects of interferon-gamma on oligodendrocytes in vitro, and the death of oligodendrocytes in an animal model of multiple sclerosis. Members of a recently characterized family of proteins, the suppressors of cytokine signaling, have been demonstrated to mediate negative cross-talk between cytokines, with induction of suppressors of cytokine signaling proteins by one cytokine inhibiting the activity of a second. Here, we assess whether induction of members of the suppressors of cytokine signaling family could explain the antagonistic biological effects of leukemia inhibitory factor and interferon-gamma upon oligodendrocytes. It is found that leukemia inhibitory factor rapidly and strongly induces the expression of suppressors of cytokine signaling-3 in cultured rat oligodendrocytes, whereas interferon-gamma weakly induces the expression of both suppressor of cytokine signaling-1 and 3. Pre-treatment of oligodendrocytes with leukemia inhibitory factor does not prevent the subsequent phosphorylation of signal transducer and activator of transcription-1 by interferon-gamma indicating that the leukemia inhibitory factor inhibition of interferon-gamma toxicity in oligodendrocytes is mediated by a suppressor of cytokine signaling-3 independent mechanism.

Original languageEnglish (US)
Pages (from-to)463-472
Number of pages10
JournalNeuroscience
Volume137
Issue number2
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

STAT1 Transcription Factor
Leukemia Inhibitory Factor
Oligodendroglia
Interferon-gamma
Cytokines
Genes
Suppressor of Cytokine Signaling Proteins
Multiple Sclerosis
Autoimmune Diseases
Animal Models
Phosphorylation

Keywords

  • Interferon gamma
  • Leukemia inhibitory factor
  • Oligodendrocyte
  • Signal transduction
  • SOCS1
  • SOCS3

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Oligodendrocytes exhibit selective expression of suppressor of cytokine signaling genes and signal transducer and activator of transcription 1 independent inhibition of interferon-gamma-induced toxicity in response to leukemia inhibitory factor",
abstract = "Multiple sclerosis is an autoimmune disease of the CNS that results in the death of oligodendrocytes, the myelinating cells of the CNS. Previous studies have indicated that the cytokine leukemia inhibitory factor prevents the cytotoxic effects of interferon-gamma on oligodendrocytes in vitro, and the death of oligodendrocytes in an animal model of multiple sclerosis. Members of a recently characterized family of proteins, the suppressors of cytokine signaling, have been demonstrated to mediate negative cross-talk between cytokines, with induction of suppressors of cytokine signaling proteins by one cytokine inhibiting the activity of a second. Here, we assess whether induction of members of the suppressors of cytokine signaling family could explain the antagonistic biological effects of leukemia inhibitory factor and interferon-gamma upon oligodendrocytes. It is found that leukemia inhibitory factor rapidly and strongly induces the expression of suppressors of cytokine signaling-3 in cultured rat oligodendrocytes, whereas interferon-gamma weakly induces the expression of both suppressor of cytokine signaling-1 and 3. Pre-treatment of oligodendrocytes with leukemia inhibitory factor does not prevent the subsequent phosphorylation of signal transducer and activator of transcription-1 by interferon-gamma indicating that the leukemia inhibitory factor inhibition of interferon-gamma toxicity in oligodendrocytes is mediated by a suppressor of cytokine signaling-3 independent mechanism.",
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T1 - Oligodendrocytes exhibit selective expression of suppressor of cytokine signaling genes and signal transducer and activator of transcription 1 independent inhibition of interferon-gamma-induced toxicity in response to leukemia inhibitory factor

AU - Emery, Ben

AU - Butzkueven, H.

AU - Snell, C.

AU - Binder, M.

AU - Kilpatrick, T. J.

PY - 2006

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N2 - Multiple sclerosis is an autoimmune disease of the CNS that results in the death of oligodendrocytes, the myelinating cells of the CNS. Previous studies have indicated that the cytokine leukemia inhibitory factor prevents the cytotoxic effects of interferon-gamma on oligodendrocytes in vitro, and the death of oligodendrocytes in an animal model of multiple sclerosis. Members of a recently characterized family of proteins, the suppressors of cytokine signaling, have been demonstrated to mediate negative cross-talk between cytokines, with induction of suppressors of cytokine signaling proteins by one cytokine inhibiting the activity of a second. Here, we assess whether induction of members of the suppressors of cytokine signaling family could explain the antagonistic biological effects of leukemia inhibitory factor and interferon-gamma upon oligodendrocytes. It is found that leukemia inhibitory factor rapidly and strongly induces the expression of suppressors of cytokine signaling-3 in cultured rat oligodendrocytes, whereas interferon-gamma weakly induces the expression of both suppressor of cytokine signaling-1 and 3. Pre-treatment of oligodendrocytes with leukemia inhibitory factor does not prevent the subsequent phosphorylation of signal transducer and activator of transcription-1 by interferon-gamma indicating that the leukemia inhibitory factor inhibition of interferon-gamma toxicity in oligodendrocytes is mediated by a suppressor of cytokine signaling-3 independent mechanism.

AB - Multiple sclerosis is an autoimmune disease of the CNS that results in the death of oligodendrocytes, the myelinating cells of the CNS. Previous studies have indicated that the cytokine leukemia inhibitory factor prevents the cytotoxic effects of interferon-gamma on oligodendrocytes in vitro, and the death of oligodendrocytes in an animal model of multiple sclerosis. Members of a recently characterized family of proteins, the suppressors of cytokine signaling, have been demonstrated to mediate negative cross-talk between cytokines, with induction of suppressors of cytokine signaling proteins by one cytokine inhibiting the activity of a second. Here, we assess whether induction of members of the suppressors of cytokine signaling family could explain the antagonistic biological effects of leukemia inhibitory factor and interferon-gamma upon oligodendrocytes. It is found that leukemia inhibitory factor rapidly and strongly induces the expression of suppressors of cytokine signaling-3 in cultured rat oligodendrocytes, whereas interferon-gamma weakly induces the expression of both suppressor of cytokine signaling-1 and 3. Pre-treatment of oligodendrocytes with leukemia inhibitory factor does not prevent the subsequent phosphorylation of signal transducer and activator of transcription-1 by interferon-gamma indicating that the leukemia inhibitory factor inhibition of interferon-gamma toxicity in oligodendrocytes is mediated by a suppressor of cytokine signaling-3 independent mechanism.

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