Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway

Wouter J. de Jonge; Esmerij P. van der Zanden; Frans O. The; Maarten F. Bijlsma; David J. van Westerloo; Roelof J. Bennink; Hans-Rudolf Berthoud; Satoshi Uematsu; Shizuo Akira; Rene M. van den Wijngaard; Guy E. Boeckxstaens

doi:https://doi.org/10.1038/ni1229

Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway

Wouter J. de Jonge, Esmerij P. van der Zanden, Frans O. The, Maarten F. Bijlsma, David J. van Westerloo, Roelof J. Bennink, Hans-Rudolf Berthoud, Satoshi Uematsu, Shizuo Akira, Rene M. van den Wijngaard, Guy E. Boeckxstaens

Research output: Contribution to journal › Article › Academic › peer-review

900 Citations (Scopus)

Abstract

Acetylcholine released by efferent vagus nerves inhibits macrophage activation. Here we show that the anti-inflammatory action of nicotinic receptor activation in peritoneal macrophages was associated with activation of the transcription factor STAT3. STAT3 was phosphorylated by the tyrosine kinase Jak2 that was recruited to the alpha 7 subunit of the nicotinic acetylcholine receptor. The anti-inflammatory effect of nicotine required the ability of phosphorylated STAT3 to bind and transactivate its DNA response elements. In a mouse model of intestinal manipulation, stimulation of the vagus nerve ameliorated surgery-induced inflammation and postoperative ileus by activating STAT3 in intestinal macrophages. We conclude that the vagal antiinflammatory pathway acts by alpha 7 subunit-mediated Jak2-STAT3 activation

Original language	English
Pages (from-to)	844-851
Journal	Nature immunology
Volume	6
Issue number	8
DOIs	https://doi.org/10.1038/ni1229
Publication status	Published - 2005

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de Jonge, W. J., van der Zanden, E. P., The, F. O., Bijlsma, M. F., van Westerloo, D. J., Bennink, R. J., Berthoud, H.-R., Uematsu, S., Akira, S., van den Wijngaard, R. M., & Boeckxstaens, G. E. (2005). Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nature immunology, 6(8), 844-851. https://doi.org/10.1038/ni1229

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title = "Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway",

abstract = "Acetylcholine released by efferent vagus nerves inhibits macrophage activation. Here we show that the anti-inflammatory action of nicotinic receptor activation in peritoneal macrophages was associated with activation of the transcription factor STAT3. STAT3 was phosphorylated by the tyrosine kinase Jak2 that was recruited to the alpha 7 subunit of the nicotinic acetylcholine receptor. The anti-inflammatory effect of nicotine required the ability of phosphorylated STAT3 to bind and transactivate its DNA response elements. In a mouse model of intestinal manipulation, stimulation of the vagus nerve ameliorated surgery-induced inflammation and postoperative ileus by activating STAT3 in intestinal macrophages. We conclude that the vagal antiinflammatory pathway acts by alpha 7 subunit-mediated Jak2-STAT3 activation",

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AU - de Jonge, Wouter J.

AU - van der Zanden, Esmerij P.

AU - The, Frans O.

AU - Bijlsma, Maarten F.

AU - van Westerloo, David J.

AU - Bennink, Roelof J.

AU - Berthoud, Hans-Rudolf

AU - Uematsu, Satoshi

AU - Akira, Shizuo

AU - van den Wijngaard, Rene M.

AU - Boeckxstaens, Guy E.

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AB - Acetylcholine released by efferent vagus nerves inhibits macrophage activation. Here we show that the anti-inflammatory action of nicotinic receptor activation in peritoneal macrophages was associated with activation of the transcription factor STAT3. STAT3 was phosphorylated by the tyrosine kinase Jak2 that was recruited to the alpha 7 subunit of the nicotinic acetylcholine receptor. The anti-inflammatory effect of nicotine required the ability of phosphorylated STAT3 to bind and transactivate its DNA response elements. In a mouse model of intestinal manipulation, stimulation of the vagus nerve ameliorated surgery-induced inflammation and postoperative ileus by activating STAT3 in intestinal macrophages. We conclude that the vagal antiinflammatory pathway acts by alpha 7 subunit-mediated Jak2-STAT3 activation

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DO - https://doi.org/10.1038/ni1229

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