Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, reduces but does not prevent, the pulmonary CD4+ effector T-cell response in a murine model of asthma

Abstract

Abstract Nuclear factor (NF)-κB is regarded as a promising target for the development of a novel therapeutic strategy in asthma. Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists inhibit the activity of NF-κB. Therefore, these agents are potent therapeutic agents for the treatment of asthma. It was found that rosiglitazone (ROS), a PPAR-γ agonist, attenuated airway inflammation in a murine model of asthma. The present study attempts to shed light on the involvement of CD4+ effector (Teff) and regulatory (Treg) T cells in the anti-asthmatic action of ROS in ovalbumin (OVA)-induced airway allergic inflammation (AAI) in BALB/c mice. We studied the effect of a 10-day treatment with ROS on the development of AAI and the absolute counts of Treg (Foxp3+CD25+CD4+) cells and activated Teff (Foxp3−CD25+CD4+) cells in the mediastinal lymph nodes (MLNs) and lungs of OVA-sensitized/challenged mice. The severity of AAI was only reduced, but not abolished, by the treatment with ROS. The absolute number of CD4+ Treg and Teff cells was increased in the MLNs and lungs of OVA-sensitized/challenged mice treated with the vehicle as compared to healthy mice. No differences were found in the count of CD4+ Treg cells between vehicle- and ROS-treated OVA-sensitized/challenged mice. The treatment with ROS reduced, but did not fully prevent, the OVA-induced increase in the count of activated CD4+ Teff cells in the MLNs and lungs. The results suggest that the impairment of the activation and clonal expansion of CD4+ Teff cells in the MLNs is involved in the anti-asthmatic action of PPAR-γ agonists. This effect does not seem to be mediated through increased recruitment of CD4+ Treg cells into the MLNs and lungs and/or local generation of Treg cells.