Inhaled calcium salts inhibit tobacco smoke-induced inflammation by modulating expression of chemokines and cytokines

Pulm Pharmacol Ther. 2018 Dec:53:86-99. doi: 10.1016/j.pupt.2018.10.004. Epub 2018 Oct 22.

Abstract

Tobacco smoke-induced lung inflammation in patients with chronic obstructive pulmonary disease (COPD) worsens with disease progression and acute exacerbations caused by respiratory infections. Chronic therapies to manage COPD center on bronchodilators to improve lung function and inhaled corticosteroids (ICS) to help reduce the risk of exacerbations. Novel therapies are needed that reduce the underlying inflammation associated with COPD and the inflammation resulting from respiratory infections that worsen disease. The lung is lined with airway surface liquid (ASL), a rheologically active material that provides an innate defense for the airway against inhaled particulate and is continuously cleared from the airways by mucociliary clearance. The rheological properties of the ASL can be altered by changes in airway hydration and by cations, such as calcium, that interact with electronegative glycoproteins. The effect of inhaled salts on inflammation resulting from tobacco smoke exposure was studied to determine if cations could be used to alter the properties of the ASL and reduce inflammation. Inhaled calcium salts, but not sodium or magnesium salts, reduced cellular inflammation and key chemokines and cytokines that were induced by tobacco smoke exposure. Similar anti-inflammatory effects of calcium salts were observed using in vitro cultures of human monocyte derived macrophages and human bronchial epithelial cells. The data suggest that inhaled calcium salts may act broadly on both biophysical and biological pathways to reduce pulmonary inflammation.

Keywords: Airway surface liquid; Anti-inflammatory; Calcium; Chronic obstructive pulmonary disease; Inhalation; Tobacco smoke.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bronchi / cytology
  • Bronchi / drug effects
  • Bronchi / pathology
  • Calcium / chemistry
  • Calcium / pharmacology*
  • Cells, Cultured
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Inflammation / etiology
  • Inflammation / prevention & control*
  • Macrophages / drug effects*
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / cytology
  • Nicotiana / toxicity
  • Pneumonia / etiology
  • Pneumonia / prevention & control
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Salts
  • Smoke / adverse effects*

Substances

  • Chemokines
  • Cytokines
  • Salts
  • Smoke
  • Calcium