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1: Nat Immunol. 2005 Aug;6(8):844-51. Epub 2005 Jul 17.Click here to read Links
Erratum in:
Nat Immunol. 2005 Sep;6(9):954.
Comment in:
Nat Immunol. 2005 Aug;6(8):756-7.

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

de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ, Berthoud HR, Uematsu S, Akira S, van den Wijngaard RM, Boeckxstaens GE.

Division of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.

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 alpha7 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 anti-inflammatory pathway acts by alpha7 subunit-mediated Jak2-STAT3 activation.

PMID: 16025117 [PubMed - indexed for MEDLINE]