title: Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients.
abstract: T-lymphocytes, including Th17-cells and T-cells expressing acetylcholine (ACh), are key components of systemic inflammation in chronic obstructive pulmonary disease (COPD). We investigated whether ACh promotes Th17 cells in COPD. ACh, IL-17A, IL-22, RORγt, FOXP3 expression and AChIL-17A, AChIL-22, AChRORγt coexpression was evaluated in peripheral blood mononuclear cells (PBMC) from COPD patients (n=16), healthy smokers (HS) (n=12) and healthy control subjects (HC) (n=13) (cultured for 48 h with PMA) by flow cytometry. Furthermore, we studied the effect of Tiotropium (Spiriva®) (100 nM) and Olodaterol (1nM) alone or in combination, and of hemicholinium-3 (50 μM) on AChIL-17A, AChIL-22, AChRORγt, and FOXP3 expression in CD3+PBT-cells of PBMC from COPD patients (n=6) cultured for 48 h with PMA. CD3+PBT-cells expressing ACh, IL-17A, IL-22 and RORγt together with CD3+PBT-cells co-expressing AChIL-17A, AChIL-22 and AChRORγt were significantly increased in COPD patients compared to HC and HS subjects with higher levels in HS than in HC without a significant difference. CD3+FOXP3+PBT-cells were increased in HS than in HC and COPD. Tiotropium and Olodaterol reduced the percentage of CD3+PBT-cells co-expressing AChIL-17A, AChIL-22, and AChRORγt while increased the CD3+FOXP3+PBT-cells in PBMC from COPD patients, cultured in vitro for 48 h, with an additive effect when used in combination. Hemicholnium-3 reduced the percentage of ACh+IL-17A+, ACh+IL-22+, and ACh+RORγt+ while it did not affect FOXP3+ expression in CD3+PBT-cells from cultured PBMC from COPD patients. We concluded that ACh might promote the increased levels of Th17-cells in systemic inflammation of COPD. Long-acting β2-agonists and anticholinergic drugs might contribute to control this event.
authors: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and the Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy. Electronic address: profita@ibim.cnr.it.
authors: Mirella
authors: M
authors: Profita
authors: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and the Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy; Dipartimento Biomedico di Medicina, Interna e Specialistica (Di.Bi.M.I.S.), Sezione di Pneumologia, University of Palermo, Palermo, Italy.
authors: Giusy Daniela
authors: GD
authors: Albano
authors: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and the Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors: Loredana
authors: L
authors: Riccobono
authors: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and the Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors: Caterina
authors: C
authors: Di Sano
authors: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and the Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors: Angela Marina
authors: AM
authors: Montalbano
authors: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and the Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors: Rosalia
authors: R
authors: Gagliardo
authors: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and the Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors: Giulia
authors: G
authors: Anzalone
authors: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and the Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors: Anna
authors: A
authors: Bonanno
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors: Michael Paul
authors: MP
authors: Pieper
authors: Unit: "Ex vivo/In vitro Models to Study the Immunopathology and the Pharmacology of Airway Diseases", Institute of Biomedicine and Molecular Immunology (IBIM), Italian National Research Council (CNR), Palermo, Italy.
authors: Mark
authors: M
authors: Gjomarkaj
mesh_terms: D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D048588:Benzoxazines / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D012307:Risk Factors; D012602:Scopolamine Derivatives / Q000494:pharmacology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D000069447:Tiotropium Bromide; D000097043:Interleukin-22
chemical_list: D000109:Acetylcholine; D048588:Benzoxazines; D018680:Cholinergic Antagonists; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide; D000097043:Interleukin-22; C418974:FOXP3 protein, human; C549647:olodaterol
keywords: Anticholinergic drugs; Beta-2 long acting; Systemic inflammation; Th-17 cells