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Mediators of Inflammation
Volume 2014, Article ID 873728, 10 pages
http://dx.doi.org/10.1155/2014/873728
Research Article

Upregulating Nonneuronal Cholinergic Activity Decreases TNF Release from Lipopolysaccharide-Stimulated RAW264.7 Cells

1Laboratory of Shock and Multiple Organ Dysfunction, Burns Institute, First Hospital Affiliated to the People’s Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China
2Department of Pathology, First Hospital Affiliated to the People’s Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China

Received 30 June 2013; Revised 3 January 2014; Accepted 16 January 2014; Published 9 March 2014

Academic Editor: Sophie Desplat-Jégo

Copyright © 2014 Yi Lv et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Nonneuronal cholinergic system plays a primary role in maintaining homeostasis. It has been proved that endogenous neuronal acetylcholine (ACh) could play an anti-inflammatory role, and exogenous cholinergic agonists could weaken macrophages inflammatory response to lipopolysaccharide (LPS) stimulation through activation of 7 subunit-containing nicotinic acetylcholine receptor ( 7nAChR). We assumed that nonneuronal cholinergic system existing in macrophages could modulate inflammation through autocrine ACh and expressed 7nAChR on the cells. Therefore, we explored whether LPS continuous stimulation could upregulate the nonneuronal cholinergic activity in macrophages and whether increasing autocrine ACh could decrease TNF release from the macrophages. The results showed that, in RAW264.7 cells incubated with LPS for 20 hours, the secretion of ACh was significantly decreased at 4 h and then gradually increased, accompanied with the enhancement of 7nAChR expression level. The release of TNF was greatly increased from RAW264.7 cells at 4 h and 8 h exposure to LPS; however, it was suppressed at 20 h. Upregulating choline acetyltransferase (ChAT) expression through ChAT gene transfection could enhance ACh secretion and reduce TNF release from the infected RAW264. 7cells. The results indicated that LPS stimulation could modulate the activity of nonneuronal cholinergic system of RAW264.7 cells. Enhancing autocrine ACh production could attenuate TNF release from RAW264.7 cells.