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Troglitazone, a PPAR-γ agonist, decreases LTC4 concentration in mononuclear cells in patients with asthma
Emilia Luczak1, Joanna Wieczfinska1, Milena Sokolowska2
1Department of Immunopathology, Medical University of Lodz, Łódź, Poland.
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.
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