PMID- 27298519 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20181113 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2016 DP - 2016 TI - Autocrine Acetylcholine, Induced by IL-17A via NFkappaB and ERK1/2 Pathway Activation, Promotes MUC5AC and IL-8 Synthesis in Bronchial Epithelial Cells. PG - 9063842 LID - 10.1155/2016/9063842 [doi] LID - 9063842 AB - 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 IkBalpha phosphorylation), Hemicholinium-3 (HCh-3) (choline uptake blocker), and Tiotropium bromide (Spiriva(R)) (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 NFkappaB and ERK1/2 pathway activation, the synthesis of ChAT, and the related activity of autocrine ACh in bronchial epithelial cells. FAU - Montalbano, Angela Marina AU - Montalbano AM AD - Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy. FAU - Albano, Giusy Daniela AU - Albano GD AD - Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy. FAU - Bonanno, Anna AU - Bonanno A AD - Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy. FAU - Riccobono, Loredana AU - Riccobono L AD - Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy. FAU - Di Sano, Caterina AU - Di Sano C AD - Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy. FAU - Ferraro, Maria AU - Ferraro M AD - Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy. FAU - Siena, Liboria AU - Siena L AD - Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy. FAU - Anzalone, Giulia AU - Anzalone G AD - 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. FAU - Gagliardo, Rosalia AU - Gagliardo R AD - Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy. FAU - Pieper, Michael Paul AU - Pieper MP AD - Boehringer Ingelheim Pharma GmbH & Co. KG, 88400 Biberach, Germany. FAU - Gjomarkaj, Mark AU - Gjomarkaj M AD - Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy. FAU - Profita, Mirella AU - Profita M AD - Institute of Biomedicine and Molecular Immunology "A. Monroy" (IBIM), National Research Council of Italy (CNR), 90146 Palermo, Italy. LA - eng PT - Journal Article DEP - 20160519 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Interleukin-17) RN - 0 (Interleukin-8) RN - 0 (MUC5AC protein, human) RN - 0 (Mucin 5AC) RN - 0 (NF-kappa B) RN - N9YNS0M02X (Acetylcholine) SB - IM MH - Acetylcholine/*metabolism MH - Autocrine Communication/drug effects MH - Bronchi/cytology MH - Cell Line MH - Epithelial Cells/*drug effects/*metabolism MH - Flow Cytometry MH - Humans MH - Interleukin-17/*pharmacology MH - Interleukin-8/*metabolism MH - MAP Kinase Signaling System/drug effects MH - Mucin 5AC/*metabolism MH - NF-kappa B/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction PMC - PMC4889862 EDAT- 2016/06/15 06:00 MHDA- 2017/05/16 06:00 PMCR- 2016/05/19 CRDT- 2016/06/15 06:00 PHST- 2016/01/07 00:00 [received] PHST- 2016/04/07 00:00 [revised] PHST- 2016/04/18 00:00 [accepted] PHST- 2016/06/15 06:00 [entrez] PHST- 2016/06/15 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] PHST- 2016/05/19 00:00 [pmc-release] AID - 10.1155/2016/9063842 [doi] PST - ppublish SO - Mediators Inflamm. 2016;2016:9063842. doi: 10.1155/2016/9063842. Epub 2016 May 19.