Autocrine Acetylcholine, Induced by IL-17A via NFκB and ERK1/2 Pathway Activation, Promotes MUC5AC and IL-8 Synthesis in Bronchial Epithelial Cells.
IL-17A is overexpressed in the lung during acute neutrophilic inflammation. Acetylcholine (ACh) increases IL-8 and Muc5AC production in airway epithelial cells. We aimed to characterize the involvement of nonneuronal components of cholinergic system on IL-8 and Muc5AC production in bronchial epithelial cells stimulated with IL-17A. Bronchial epithelial cells were stimulated with recombinant human IL-17A (rhIL-17A) to evaluate the ChAT expression, the ACh binding and production, the IL-8 release, and the Muc5AC production. Furthermore, the effectiveness of PD098,059 (inhibitor of MAPKK activation), Bay11-7082 (inhibitor of IkBα phosphorylation), Hemicholinium-3 (HCh-3) (choline uptake blocker), and Tiotropium bromide (Spiriva®) (anticholinergic drug) was tested in our in vitro model. We showed that rhIL-17A increased the expression of ChAT, the levels of ACh binding and production, and the IL-8 and Muc5AC production in stimulated bronchial epithelial cells compared with untreated cells. The pretreatment of the cells with PD098,059 and Bay11-7082 decreased the ChAT expression and the ACh production/binding, while HCh-3 and Tiotropium decreased the IL-8 and Muc5AC synthesis in bronchial epithelial cells stimulated with rhIL-17A. IL-17A is involved in the IL-8 and Muc5AC production promoting, via NFκB and ERK1/2 pathway activation, the synthesis of ChAT, and the related activity of autocrine ACh in bronchial epithelial cells.
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy.
Angela Marina
AM
Montalbano
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy.
Giusy Daniela
GD
Albano
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy.
Anna
A
Bonanno
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy.
Loredana
L
Riccobono
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy.
Caterina
C
Di Sano
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy.
Maria
M
Ferraro
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy.
Liboria
L
Siena
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy; Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BioNec), 90127 Palermo, Italy.
Giulia
G
Anzalone
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy.
Rosalia
R
Gagliardo
Boehringer Ingelheim Pharma GmbH & Co. KG, 88400 Biberach, Germany.
Michael Paul
MP
Pieper
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy.
Mark
M
Gjomarkaj
Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy.
Mirella
M
Profita
D000109:Acetylcholine / Q000378:metabolism*; D019898:Autocrine Communication / Q000187:drug effects; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D055271:Mucin 5AC / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020381:Interleukin-17; D016209:Interleukin-8; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D016328:NF-kappa B; D000109:Acetylcholine