Troglitazone, a PPAR-γ agonist, decreases LTC 4 concentration in mononuclear cells in patients with asthma

Pharmacol Rep. 2017 Dec;69(6):1315-1321. doi: 10.1016/j.pharep.2017.05.006. Epub 2017 May 24.

Abstract

Background: Asthma is an inflammatory disorder with multiple mediators involved in the inflammatory response. Despite several attempts, no new anti-inflammatory drugs have been registered for asthma treatment for several years. However, thiazolidinediones, peroxisome proliferator-activated receptor agonists, have demonstrated some anti-inflammatory properties in various experimental settings. The aim of this study was to assess the influence of troglitazone on LTC4 and 15-HETE concentrations. It also evaluates TNF-induced eotaxin synthesis in peripheral blood mononuclear cells from 14 patients with mild asthma and 13 healthy controls.

Methods: PBMCs were isolated from the whole blood of the asthmatics and healthy subjects and pretreated with 0.1, 1 or 10μM of Troglitazone. The cells were then exposed to 10-6M calcium jonophore or 10ng/ml TNF. The production and release of LTC4, 15-HETE and eotaxin were then assessed.

Results: Troglitazone caused a dose-dependent inhibition in LTC4 synthesis in both asthmatics and healthy subjects. Troglitazone did not influence 15-HETE or eotaxin production in either asthmatic patients or in healthy individuals.

Conclusion: Due to its inhibition of LTC4 synthesis, troglitazone therapy is an interesting potential therapeutic approach in asthma and other LTC4 related inflammatory disorders.

Keywords: Asthma; PPAR-γ; Troglitazone.

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Asthma / drug therapy*
  • Case-Control Studies
  • Chromans / administration & dosage
  • Chromans / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Leukotriene C4 / biosynthesis
  • Male
  • Middle Aged
  • PPAR gamma / agonists
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / pharmacology*
  • Troglitazone
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Chromans
  • Hypoglycemic Agents
  • PPAR gamma
  • Thiazolidinediones
  • Leukotriene C4
  • Troglitazone