PMID- 21665296
OWN - NLM
STAT- MEDLINE
DCOM- 20110913
LR  - 20131121
IS  - 1872-8421 (Electronic)
IS  - 0165-5728 (Linking)
VI  - 236
IP  - 1-2
DP  - 2011 Jul
TI  - Cholinergic modulation of dendritic cell function.
PG  - 47-56
LID - 10.1016/j.jneuroim.2011.05.007 [doi]
AB  - Dendritic cells (DCs) are highly specialized antigen-presenting cells with a 
      unique ability to activate resting T lymphocytes. Acetylcholine (ACh) is the 
      primary parasympathetic neurotransmitter and also a non-neural paracrine factor 
      produced by different cells. Here, we analyzed the expression of the cholinergic 
      system in DCs. We found that DCs express the muscarinic receptors M(3), M(4) and 
      M(5), as well as the enzymes responsible for the synthesis and degradation of 
      ACh, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), 
      respectively. Differentiation of DCs in the presence of the cholinergic agonist 
      carbachol, the synthetic analog of ACh, resulted in an increased expression of 
      HLA-DR and CD86 and the stimulation of TNF-alpha and IL-8 production. All these 
      effects were prevented by atropine, a muscarinic ACh receptor (mAChR) antagonist. 
      Carbachol, was also able to modulate the function of DCs when added after the 
      differentiation is accomplished; it increased the expression of HLA-DR, improved 
      the T cell priming ability of DCs, and stimulated the production of TNF-alpha but not 
      IL-12 or IL-10. By contrast, carbachol significantly inhibited the stimulation of 
      HLA-DR expression and the enhancement in the T cell priming ability of DCs 
      triggered by LPS. Interestingly, the TNF-alpha antagonist etanercept completely 
      prevented the increased expression of HLA-DR induced by carbachol, suggesting 
      that it promotes the phenotypic maturation of DCs by stimulating the production 
      of TNF-alpha. ACh induced similar effects than carbachol; it stimulated the 
      expression of HLA-DR and the production of TNF-alpha, while inhibiting the 
      stimulation of HLA-DR expression and IL-12 production triggered by LPS. 
      Similarly, neostigmine, an inhibitor of AChE, also stimulated the expression of 
      HLA-DR and the production of TNF-alpha by DCs while inhibiting the production of 
      TNF-alpha and IL-12 triggered by LPS. These results support the existence of an 
      autocrine/paracrine loop through which ACh modulates the function of DCs.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Salamone, Gabriela
AU  - Salamone G
AD  - Departamento de Inmunologia, Instituto de Investigaciones Hematologicas and 
      Instituto de Estudios Oncologicos Fundacion Maissa, Academia Nacional de 
      Medicina, Argentina. salamone.gabriela@gmail.com
FAU - Lombardi, Gabriela
AU  - Lombardi G
FAU - Gori, Soledad
AU  - Gori S
FAU - Nahmod, Karen
AU  - Nahmod K
FAU - Jancic, Carolina
AU  - Jancic C
FAU - Amaral, Maria Marta
AU  - Amaral MM
FAU - Vermeulen, Monica
AU  - Vermeulen M
FAU - Espanol, Alejandro
AU  - Espanol A
FAU - Sales, Maria Elena
AU  - Sales ME
FAU - Geffner, Jorge
AU  - Geffner J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110612
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Cholinergic Agonists)
RN  - 0 (Cholinergic Antagonists)
RN  - 0 (Receptors, Muscarinic)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/*physiology
MH  - Acetylcholinesterase/physiology
MH  - Cell Differentiation/drug effects/physiology
MH  - Cells, Cultured
MH  - Choline O-Acetyltransferase/physiology
MH  - Cholinergic Agonists/*pharmacology
MH  - Cholinergic Antagonists/*pharmacology
MH  - Dendritic Cells/*drug effects/metabolism/*physiology
MH  - Humans
MH  - Male
MH  - Receptors, Muscarinic/physiology
EDAT- 2011/06/15 06:00
MHDA- 2011/09/14 06:00
CRDT- 2011/06/14 06:00
PHST- 2011/02/01 00:00 [received]
PHST- 2011/05/03 00:00 [revised]
PHST- 2011/05/14 00:00 [accepted]
PHST- 2011/06/14 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2011/09/14 06:00 [medline]
AID - S0165-5728(11)00137-8 [pii]
AID - 10.1016/j.jneuroim.2011.05.007 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2011 Jul;236(1-2):47-56. doi: 10.1016/j.jneuroim.2011.05.007. 
      Epub 2011 Jun 12.