Interferon-γ Up-regulates Expression of Cysteinyl Leukotriene Type 2 Receptors on Eosinophils in Asthmatic Patients

Abstract

Cysteinyl leukotrienes (cysLTs) are strong bronchoconstrictive mediators that play a key role in asthma inflammation. They act through specific receptors including cysLT type 1 receptor (CysLT1R) and cysLT type 2 receptor (CysLT2R). Although these two receptors are co-expressed on inflammatory cells, little is known about CysLT2R in patients with asthma. The aims of this study were to investigate the changes in cysLT receptors (CysLTRs) during asthma exacerbations and to determine which cytokine modulates CysLTR expression on eosinophils. We assessed protein expression and messenger RNA of CysLT1R and CysLT2R in peripheral blood eosinophils and measured urinary leukotriene E(4) levels in 36 patients with stable asthma, 23 subjects with asthma exacerbation, and 15 healthy subjects. We also evaluated the modulation of these receptors by interleukin (IL)-1beta, IL-4, IL-5, IL-13, interferon (IFN)-gamma and tumor necrosis factor-alpha in cultured eosinophils. Expression of both CysLT1R and CysLT2R on eosinophils during asthma exacerbations was significantly higher (p < 0.05) than in stable asthma and healthy subjects. A greater expression of CysLT2R in exacerbation was found in nonatopic asthmatics. Only IFN-gamma up-regulated cell-surface expression of CysLT2R in a dose-dependent manner and enhanced messenger RNA levels. No cytokine affected CysLT1R expression or messenger RNA level. CysLT2R expression on eosinophils was increased in patients, especially in nonatopic subjects, during asthma exacerbation, and was up-regulated by IFN-gamma; therefore we speculate that a pathway through CysLT2R might modulate exacerbations of asthma.