PGE(2) decreases muscle cell proliferation in patients with non-asthmatic eosinophilic bronchitis

Prostaglandins Other Lipid Mediat. 2011 Aug;95(1-4):11-8. doi: 10.1016/j.prostaglandins.2011.03.002. Epub 2011 Mar 30.

Abstract

Non-asthmatic eosinophilic bronchitis (NAEB) is characterized by chronic cough and sputum eosinophilia without bronchial hyperresponsiveness. The aim of the present study is to determine whether increased levels of PGE(2) from NAEB sputum supernatants play a protective role in airway inflammation and muscular hyperplasia. Twenty-one patients with NAEB, 15 asthmatic patients, and 12 healthy subjects were studied. An up-regulated PGE(2) enzymatic pathway was observed in bronchial biopsies from patients with NAEB as compared with samples from asthmatic patients. Also, EP2 and EP4 receptor expression was increased in these samples. BSMC proliferation was inhibited to a greater extent in NAEB sputum supernatants than in those taken from asthmatic subjects and healthy controls. This inhibition was mostly due to PGE(2) levels, a fact which was confirmed by employing synthetic EP2 and EP4 agonist and antagonist receptors.These findings suggest that PGE(2) inhibits BSMC proliferation entailing a reduction of smooth muscle hyperplasia and thus protecting against the onset of airflow obstruction.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asthma / enzymology
  • Asthma / metabolism
  • Asthma / pathology
  • Biopsy
  • Bronchi / pathology
  • Bronchitis, Chronic / metabolism
  • Bronchitis, Chronic / pathology*
  • Case-Control Studies
  • Cell Proliferation*
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Dinoprostone / pharmacology*
  • Dinoprostone / physiology
  • Eosinophilia / metabolism
  • Eosinophilia / pathology*
  • Female
  • Gene Expression
  • Humans
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism
  • Male
  • Middle Aged
  • Myocytes, Smooth Muscle / pathology*
  • Phospholipases A2, Cytosolic / genetics
  • Phospholipases A2, Cytosolic / metabolism
  • Phospholipases A2, Secretory / genetics
  • Phospholipases A2, Secretory / metabolism
  • Prostaglandin-E Synthases
  • Receptors, Prostaglandin E, EP2 Subtype / genetics
  • Receptors, Prostaglandin E, EP2 Subtype / metabolism
  • Receptors, Prostaglandin E, EP4 Subtype / genetics
  • Receptors, Prostaglandin E, EP4 Subtype / metabolism
  • Sputum / enzymology
  • Young Adult

Substances

  • Cytokines
  • PTGER2 protein, human
  • PTGER4 protein, human
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Cyclic AMP
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Phospholipases A2, Cytosolic
  • Phospholipases A2, Secretory
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • Dinoprostone