Stimulation of the vagus nerve attenuates macrophage activity by activating the JAK- 2-STAT-3 signaling pathway
نویسندگان
چکیده
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 antiinflammatory pathway acts by alpha7 subunit-mediated Jak2-STAT3 activation. van de Zanden.indb 40 23-5-2011 11:43:44 41 Vagal anti-inflammatory pathway mediated via JAK2-STAT3 activation
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