Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice

Possible involvement of Stat3 activation in the protection of neurons

Toru Yamashita, Kazunobu Sawamoto, Shigeaki Suzuki, Norihiro Suzuki, Kazuhide Adachi, Takeshi Kawase, Masahiko Mihara, Yoshiyuki Ohsugi, Koji Abet, Hideyuki Okano

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Interleukin (IL)-6 expression transiently increases in the acute phase of cerebral ischemia. To investigate the physiological significance of endogenous IL-6 expression and to identify the main signal pathway for the action of IL-6, we administered anti-mouse IL-6 receptor monoclonal antibody (IL-6RA), which blocks IL-6 signaling, to mice immediately after a 45-min period of middle cerebral artery occlusion (MCAO). At 6 h after MCAO, IL-6RA administration had resulted in a significant reduction in the amount of phosphorylated signal transducer and activator of transcription-3 (Stat3) protein in the peri-infarct area of the cortex. At 24 h after MCAO, blockade of IL-6 signaling had led to an increase in number of apoptotic cells in the peri-infarct area and enlargement of the size of the infarct, and it had adversely affected neurological function. These results suggest that endogenous IL-6 plays a critical role in preventing damaged neurons from undergoing apoptosis in the acute phase of cerebral ischemia and that its role may be mediated by Stat3 activation.

Original languageEnglish
Pages (from-to)459-468
Number of pages10
JournalJournal of Neurochemistry
Volume94
Issue number2
DOIs
Publication statusPublished - Jul 2005

Fingerprint

STAT3 Transcription Factor
Transcriptional Activation
Neurons
Interleukin-6
Chemical activation
Middle Cerebral Artery Infarction
Brain Ischemia
STAT Transcription Factors
Interleukin-6 Receptors
Interleukins
Neuroprotection
Signal Transduction
Cell Count
Monoclonal Antibodies
Cells
Apoptosis
Proteins

Keywords

  • Focal cerebral ischemia
  • Interleukin-6
  • Interleukin6 receptor antibody
  • Neuroprotection
  • Signal transducer and activation of transcription-3

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice : Possible involvement of Stat3 activation in the protection of neurons. / Yamashita, Toru; Sawamoto, Kazunobu; Suzuki, Shigeaki; Suzuki, Norihiro; Adachi, Kazuhide; Kawase, Takeshi; Mihara, Masahiko; Ohsugi, Yoshiyuki; Abet, Koji; Okano, Hideyuki.

In: Journal of Neurochemistry, Vol. 94, No. 2, 07.2005, p. 459-468.

Research output: Contribution to journalArticle

Yamashita, Toru ; Sawamoto, Kazunobu ; Suzuki, Shigeaki ; Suzuki, Norihiro ; Adachi, Kazuhide ; Kawase, Takeshi ; Mihara, Masahiko ; Ohsugi, Yoshiyuki ; Abet, Koji ; Okano, Hideyuki. / Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice : Possible involvement of Stat3 activation in the protection of neurons. In: Journal of Neurochemistry. 2005 ; Vol. 94, No. 2. pp. 459-468.
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