The vagus nerve as a modulator of intestinal inflammation - TI Pharma

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5 CHAPTER Vagus nerve activity augments intestinal macrophage phagocytosis via nicotinic acetylcholine receptor alpha4beta2 Esmerij P van der Zanden Susanne A Snoek Sigrid E Heinsbroek Oana I Stanisor Caroline Verseijden Guy E Boeckxstaens Maikel P Peppelenbosch David R Greaves Siamon Gordon Wouter J de Jonge Gastroenterology. 2009 Sep;137(3):1029-39, 1039.
Chapter 5 ABSTRACT Background and Aims: the vagus nerve negatively regulates macrophage cytokine production via the release of acetylcholine (ACh) and activation of nicotinic acetylcholine receptors (nAChR). In various models of intestinal inflammation, vagus nerve efferent stimulation ameliorates disease. Given the actively constrained cytokine responses of intestinal macrophages, we explored the effect of nAChR activation on endo- and phagocytosis by macrophages residing in the peritoneal and mucosal compartment. Methods: the phagocytic uptake by intestinal and peritoneal macrophages was measured by FACS analysis, and the nAChR involved was determined by pharmacological blockade, shRNA-assisted gene knockdown and the use of specific nAChR KO mice. The effect of electrical vagus nerve stimulation on epithelial translocation and macrophage uptake of luminal particles was studied in mice. Results: in isolated intestinal and peritoneal macrophages, nAChR activation enhanced endocytosis and phagocytosis. This effect was mediated via stimulated recruitment of GTPase Dynamin-2 to the forming phagocytic cup. These effects involve nAChR α4/β2, rather than nAChR α7. Despite enhanced bacterial uptake, acetylcholine reduced NF-κB activation and pro-inflammatory cytokine production, while stimulating anti-inflammatory IL10 production. Vagus nerve stimulation in mice altered mucosal immune responses by augmenting epithelial transport and uptake of luminal bacteria by lamina propria macrophages. Conclusions: acetylcholine enhances phagocytic potential while inhibiting immune reactivity via nAChR α4/β2 in mouse macrophages. Hence, vagus nerve efferent activity may stimulate surveillance in the intestinal mucosa and peritoneal compartment. 78
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Promotiecommissie Promotores: Prof.
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Table of contents Chapter 1 Introdu
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Introduction and outline The aim of
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Introduction and outline Hence, the
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Introduction and outline 18. van de
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Chapter 2 ABSTRACT The cholinergic
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Chapter 2 neurotransmitter ACh with
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Chapter 2 THE VAGUS NERVE AND CHOLI
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Page 25 and 26: Chapter 2 unclear whether this hybr
Page 27 and 28: Chapter 2 reduction of NF-κB activ
Page 29 and 30: Chapter 2 CONCLUDING REMARKS The hy
Page 31 and 32: Chapter 2 34 17. The FO, Boeckxstae
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Page 37 and 38: Chapter 3 ABSTRACT Acetylcholine re
Page 39 and 40: Chapter 3 by bowel manipulation 12
Page 41 and 42: Chapter 3 for preparation of whole
Page 43 and 44: Chapter 3 Figure 1. Nicotine attenu
Page 45 and 46: Chapter 3 Figure 2. Inhibition of m
Page 47 and 48: Chapter 3 macrophage cell lysates s
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Page 55 and 56: Chapter 3 Activation of the STAT3 c
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Page 59 and 60: 4 CHAPTER Deciphering STAT3 signali
Page 61 and 62: INTRODUCTION Deciphering STAT3 sign
Page 63 and 64: Deciphering STAT3 signaling in chol
Page 69 and 70: DISCUSSION Deciphering STAT3 signal
Page 71: REFERENCES Deciphering STAT3 signal
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Page 77 and 78: Chapter 5 described previously 6 .
Page 79 and 80: Chapter 5 Figure 1 Cholinergic agon
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Page 85 and 86: Chapter 5 Zymosan induced formation
Page 87 and 88: Chapter 5 marker CD11 c (Fig. 7E),
Page 89 and 90: Chapter 5 Our data demonstrate that
Page 91 and 92: Chapter 5 REFERENCE LIST 96 1. Boro
Page 93 and 94: Thesis E.P.M. van der Zanden The va
Page 95 and 96: Summary and conclusions The goal of
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Page 111 and 112: Chapter 7 18. Yu Z, Zhang W, Kone B
Page 113 and 114: Shizuo Akira Department of Host Def
Page 115 and 116: List of publications
Page 117 and 118: Dankwoord
Page 119 and 120: om de ene keer olijfolie te drinken
Page 121: Curriculum Vitae Curriculum Vitae E
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