Release of ciliary neurotrophic factor from cultured astrocytes and its modulation by cytokines

Hiroyuki Kamiguchi, Kazunari Yoshida, Masachika Sagoh, Hikaru Sasaki, Makoto Inaba, Hirooki Wakamoto, Mitsuhiro Otani, Shigeo Toya

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

CNTF rescues various types of lesioned neurons in vivo, and it needs to be released from astrocytes into the extracellular space to have the effect. However, direct evidence for CNTF release has not been unequivocally demonstrated. We hypothesized that the rapid sequestration by CNTF receptor present on cultured astrocytes might be the cause of the inability to detect CNTF released into astrocyte-conditioned medium (ACM). Therefore, we measured CNTF immunoreactivity in medium conditioned by astrocytes treated with phosphatidylinositol-specific phospholipase C (PI-PLC) which was used to prevent released CNTF from binding to the CNTF receptor, since PI-PLC cleaves glycosyl-phosphatidylinositol anchor of CNTFRα, the unique component involved in CNTF binding. CNTF was not detectable in untreated ACM, but was detectable in PI-PLC-treated ACM. These results together with the evidence that PI-PLC treatment did not have a toxic effect on astrocytes prove the fact that CNTF can be released from astrocytes without cell lysis. Subsequently, the effect of cytokines such as IL-1β, TNF-α, and EGF on CNTF release was examined. These cytokines increased CNTF protein levels in ACMs without increasing CNTF protein levels in astrocyte-extracts, indicating that they enhanced CNTF release from astrocytes.

Original languageEnglish
Pages (from-to)1187-1193
Number of pages7
JournalNeurochemical Research
Volume20
Issue number10
DOIs
Publication statusPublished - 1995 Oct

Fingerprint

Ciliary Neurotrophic Factor
Astrocytes
Modulation
Cytokines
Phosphoinositide Phospholipase C
Conditioned Culture Medium
Ciliary Neurotrophic Factor Receptor
Glycosylphosphatidylinositols
Poisons
Extracellular Space
Anchors
Interleukin-1
Epidermal Growth Factor
Neurons

Keywords

  • astrocyte
  • Ciliary neurotrophic factor (CNTF)
  • CNTF receptor
  • cytokine
  • enzyme immunoassay
  • phosphatidylinositolspecific phospholipase C

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

Cite this

Release of ciliary neurotrophic factor from cultured astrocytes and its modulation by cytokines. / Kamiguchi, Hiroyuki; Yoshida, Kazunari; Sagoh, Masachika; Sasaki, Hikaru; Inaba, Makoto; Wakamoto, Hirooki; Otani, Mitsuhiro; Toya, Shigeo.

In: Neurochemical Research, Vol. 20, No. 10, 10.1995, p. 1187-1193.

Research output: Contribution to journalArticle

Kamiguchi, Hiroyuki ; Yoshida, Kazunari ; Sagoh, Masachika ; Sasaki, Hikaru ; Inaba, Makoto ; Wakamoto, Hirooki ; Otani, Mitsuhiro ; Toya, Shigeo. / Release of ciliary neurotrophic factor from cultured astrocytes and its modulation by cytokines. In: Neurochemical Research. 1995 ; Vol. 20, No. 10. pp. 1187-1193.
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