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- Title
Olodaterol exerts anti-inflammatory effects on COPD airway epithelial cells.
- Authors
Yang, Nan; Singhera, Gurpreet K.; Yan, Yi Xuan; Pieper, Michael P.; Leung, Janice M.; Sin, Don D.; Dorscheid, Delbert R.
- Abstract
<bold>Background: </bold>Airway inflammation is a key feature of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroids (ICS) remain the main treatment for airway inflammation. Studies have noted the increased efficacy of ICS and long-acting beta 2 agonist (LABA) combination therapy in controlling exacerbations and improving airway inflammation than either monotherapy. Further studies have suggested that LABAs may have inherent anti-inflammatory potential, but this has not been well-studied.<bold>Objective: </bold>We hypothesize that the LABA olodaterol can inhibit airway inflammation resulting from exposure to respiratory syncytial virus (RSV) via its binding receptor, the β2-adrenergic receptor.<bold>Methods: </bold>Human bronchial epithelial brushing from patients with and without COPD were cultured into air-liquid interface (ALI) cultures and treated with or without olodaterol and RSV infection to examine the effect on markers of inflammation including interleukin-8 (IL-8) and mucus secretion. The cell line NCI-H292 was utilized for gene silencing of the β2-adrenergic receptor via siRNA as well as receptor blocking via ICI 118,551 and butaxamine.<bold>Results: </bold>At baseline, COPD-ALIs produced greater amounts of IL-8 than control ALIs. Olodaterol reduced RSV-mediated IL-8 secretion in both COPD and control ALIs and also significantly reduced Muc5AC staining in COPD-ALIs infected with RSV. A non-significant reduction was seen in control ALIs. Gene silencing of the β2-adrenergic receptor in NCI-H292 negated the ability of olodaterol to inhibit IL-8 secretion from both RSV infection and lipopolysaccharide stimulus, as did blocking of the receptor with ICI 118,551 and butaxamine.<bold>Conclusions: </bold>Olodaterol exhibits inherent anti-inflammatory properties on the airway epithelium, in addition to its bronchodilation properties, that is mediated through the β2-adrenergic receptor and independent of ICS usage.
- Subjects
EPITHELIAL cells; ADRENERGIC receptors; ADRENERGIC beta agonists; OBSTRUCTIVE lung diseases; AIRWAY (Anatomy); GENE silencing; RESPIRATORY mucosa; CELL culture; HETEROCYCLIC compounds; INFLAMMATION; BRONCHODILATOR agents; INHALATION administration
- Publication
Respiratory Research, 2021, Vol 22, Issue 1, p1
- ISSN
1465-9921
- Publication type
journal article
- DOI
10.1186/s12931-021-01659-2