Abstract
Acetylcholine (ACh) is the main mediator associated with the anti-inflammatory cholinergic pathway. ACh plays an inhibitory role in several inflammatory conditions. Sepsis is a severe clinical syndrome characterized by bacterial dissemination and overproduction of inflammatory mediators. The aim of the current study was to investigate the participation of endogenous ACh in the modulation of inflammatory response induced by a model of polymicrobial sepsis. Wild type (WT) and vesicular acetylcholine transporter knockdown (VAChTKD) mice were exposed to cecal ligation and perforation- induced sepsis. Levels of Tumor Necrosis Factor Alpha (TNF-α) and bacterial growth in peritoneal cavity and serum, and neutrophil recruitment into peritoneal cavity were assessed. The concentration of TNF-α in both compartments was higher in VAChTKD in comparison with WT mice. VAChTKD mice presented elevated burden of bacteria in peritoneum and blood, and impairment of neutrophil migration to peritoneal cavity. This phenotype was reversed by treatment with nicotine salt. These findings suggest that endogenous ACh plays a major role in the control of sepsis-associated inflammatory response.
Keywords: Acetylcholine, nicotine, sepsis, inflammation, neutrophils.
Current Neurovascular Research
Title:Endogenous Acetylcholine Controls the Severity of Polymicrobial Sepsisassociated Inflammatory Response in Mice
Volume: 13 Issue: 1
Author(s): Flávio Almeida Amaral, Caio Tavares Fagundes, Aline Silva Miranda, Vivian Vasconceios Costa, Livia Resende, Danielle da Gloria de Souza, Vania Ferreira Prado, Mauro Martins Teixeira, Marco Antonio Maximo Prado and Antonio Lucio Teixeira
Affiliation:
Keywords: Acetylcholine, nicotine, sepsis, inflammation, neutrophils.
Abstract: Acetylcholine (ACh) is the main mediator associated with the anti-inflammatory cholinergic pathway. ACh plays an inhibitory role in several inflammatory conditions. Sepsis is a severe clinical syndrome characterized by bacterial dissemination and overproduction of inflammatory mediators. The aim of the current study was to investigate the participation of endogenous ACh in the modulation of inflammatory response induced by a model of polymicrobial sepsis. Wild type (WT) and vesicular acetylcholine transporter knockdown (VAChTKD) mice were exposed to cecal ligation and perforation- induced sepsis. Levels of Tumor Necrosis Factor Alpha (TNF-α) and bacterial growth in peritoneal cavity and serum, and neutrophil recruitment into peritoneal cavity were assessed. The concentration of TNF-α in both compartments was higher in VAChTKD in comparison with WT mice. VAChTKD mice presented elevated burden of bacteria in peritoneum and blood, and impairment of neutrophil migration to peritoneal cavity. This phenotype was reversed by treatment with nicotine salt. These findings suggest that endogenous ACh plays a major role in the control of sepsis-associated inflammatory response.
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Amaral Almeida Flávio, Fagundes Tavares Caio, Miranda Silva Aline, Costa Vasconceios Vivian, Resende Livia, Gloria de Souza da Danielle, Prado Ferreira Vania, Teixeira Martins Mauro, Maximo Prado Antonio Marco and Teixeira Lucio Antonio, Endogenous Acetylcholine Controls the Severity of Polymicrobial Sepsisassociated Inflammatory Response in Mice, Current Neurovascular Research 2016; 13 (1) . https://dx.doi.org/10.2174/1567202612666151026105915
DOI https://dx.doi.org/10.2174/1567202612666151026105915 |
Print ISSN 1567-2026 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5739 |
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