Cigarette smoke extract (CSE) promotes acetylcholine (ACh) mediated inflammation and oxidative stress by PEBP1/Raf-mediated MEK and ERK pathway in human bronchial epithelial cells
Giusy D Albano (Palermo, Italy), Giusy D. Albano, Anna Bonanno, Loredana Riccobono, Rosalia Gagliardo, Michael Pieper, Mark Gjomarkaj, Mirella Profita
Source: International Congress 2015 – New data on established treatments for asthma and COPD
Session: New data on established treatments for asthma and COPD
Session type: Thematic Poster Session
Number: 1015
Disease area: Airway diseases
Abstract Chronic cigarette smoking can activate inflammation and oxidative/nitrosative stress often increasing expression of non neuronal cholinergic system in epithelial cells. PEBP1 binds to Raf, inhibiting Raf-mediated MEK and ERK pathway regulating the mechanism of oxidative stress and inflammation.We aimed to investigate whether the long term exposure to CSE (0 to 20% for 7 days) promotes inflammation and oxidative/nitrosative stress by autocrine ACh production and via PEBP1 Raf-mediated MEK and ERK pathway activation in bronchial epithelial cell line (16HBE).We evaluated the ACh binding and Ros production by flowcytometry, Choline Acetyltransferase (ChAT), NOX4, PEBP1and ERk1/2 phosphorylation by western blot, the IL-8 release by ELISA, in 16HBE CSE treated. The effect of Tiotropium (Spiriva®), Olodaterol and Hemicholinium (HCh) a potent choline uptake blocker was tested.We showed increased levels of ChAT, autocrine ACh binding, pPEBP1, pERK1/2, Ros, NOX4 and IL-8 in CSE treated 16HBE compared to untreated cells. HCh, reducing levels of autocrine ACh synthesis and binding, downregulated PEBP1 and ERK1/2 phosphorylation as well as Ros, Nox4 and IL-8 production in CSE treated cells. Tiotropium (Spiriva®) or Olodaterol are able to reduce the levels of Ros, NoX4, IL-8 and ACh binding.Cigarette smoke, promoting the synthesis of autocrine ACh, generates the detachment of PEBP1 to Raf, increasing Raf-mediated MEK and ERK pathway activation and the related inflammatory and oxidative mediators in epithelium. Anticholinergic and long-acting b 2-agonist drugs are able to control these mechanisms.
Rating:
You must login to grade this presentation.
Share or cite this content
Citations should be made in the following way:
Giusy D Albano (Palermo, Italy), Giusy D. Albano, Anna Bonanno, Loredana Riccobono, Rosalia Gagliardo, Michael Pieper, Mark Gjomarkaj, Mirella Profita. Cigarette smoke extract (CSE) promotes acetylcholine (ACh) mediated inflammation and oxidative stress by PEBP1/Raf-mediated MEK and ERK pathway in human bronchial epithelial cells. Eur Respir J 2015; 46: Suppl. 59, 1015
You must login to share this Presentation/Article on Twitter, Facebook, LinkedIn or by email.
Member's Comments
Related content which might interest you:
Related content which might interest you: