title: Dysregulated Homeostasis of Acetylcholine Levels in Immune Cells of RR-Multiple Sclerosis Patients.
abstract: Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNFα, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis.
authors.affiliation: Department of Biology and Biotechnologies Charles Darwin, Research, Center of Neurobiology Daniel Bovet, Sapienza University of Rome, 00185 Rome, Italy. maria.dibari@uniroma1.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bari
authors.affiliation: Department of Medical, Oral and Biotechnological Science, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy. mreale@unich.it.
authors.forename: Marcella
authors.initials: M
authors.lastname: Reale
authors.affiliation: Department of Medical, Oral and Biotechnological Science, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy. marta.dinicola@unich.it.
authors.forename: Marta
authors.initials: M
authors.lastname: Di Nicola
authors.affiliation: Department of Biology and Biotechnologies Charles Darwin, Research, Center of Neurobiology Daniel Bovet, Sapienza University of Rome, 00185 Rome, Italy. viviana.orlando@uniroma1.it.
authors.forename: Viviana
authors.initials: V
authors.lastname: Orlando
authors.affiliation: Department of Biology and Biotechnologies Charles Darwin, Research, Center of Neurobiology Daniel Bovet, Sapienza University of Rome, 00185 Rome, Italy. galiziasabrina1@gmail.com.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Galizia
authors.affiliation: School of Hygiene and Preventive Medicine, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy. porfilioitalo@gmail.com.
authors.forename: Italo
authors.initials: I
authors.lastname: Porfilio
authors.affiliation: Department of Medical, Oral and Biotechnological Science, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy. erica.costantini@unich.it.
authors.forename: Erica
authors.initials: E
authors.lastname: Costantini
authors.affiliation: Department of Medical, Oral and Biotechnological Science, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy. chiara.dangelo@unich.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: D'Angelo
authors.affiliation: Department of Neurology and Psichiatry, Sapienza University of Rome, 00185 Rome, Italy. serena.ruggieri@gmail.com.|Department of Neurosciences, San Camillo Forlanini Hospital, 00185 Rome, Italy. serena.ruggieri@gmail.com.
authors.forename: Serena
authors.initials: S
authors.lastname: Ruggieri
authors.affiliation: Department of Biology and Biotechnologies Charles Darwin, Research, Center of Neurobiology Daniel Bovet, Sapienza University of Rome, 00185 Rome, Italy. stefano.biagioni@uniroma1.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Biagioni
authors.affiliation: Department of Neurosciences, San Camillo Forlanini Hospital, 00185 Rome, Italy. c.gasperini@libero.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gasperini
authors.affiliation: Department of Biology and Biotechnologies Charles Darwin, Research, Center of Neurobiology Daniel Bovet, Sapienza University of Rome, 00185 Rome, Italy. adamaria.tata@uniroma1.it.
authors.forename: Ada Maria
authors.initials: AM
authors.lastname: Tata
mesh_terms: D000109:Acetylcholine / Q000097:blood*; D000110:Acetylcholinesterase / Q000378:metabolism; D000328:Adult; D000368:Aged; D002091:Butyrylcholinesterase / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D016207:Cytokines; D020382:Interleukin-18; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D000109:Acetylcholine
keywords: acetylcholine; acetylcholinesterase; butyrylcholinesterase; cytokines; multiple sclerosis