Rosiglitazone, a peroxisome proliferator-activated receptor-γ agonist, attenuates airway inflammation by inhibiting the proliferation of effector T cells in a murine model of neutrophilic asthma.

Abstract

An imbalanced Th17-mediated immune response contributes substantially to neutrophilic asthma. Studies have also demonstrated that peroxisome proliferator-activated receptor-γ (PPARγ) plays a critical role in inflammatory disease. However, the effect of PPARγ on airway inflammation in neutrophilic asthma remains unclear. In the current study, we evaluated the potential therapeutic role of rosiglitazone (RSG) in a new mouse model of asthma characterised by increased neutrophils rather than eosinophils. A co-culture system of DCs with CD4+ naïve T cells was established to evaluate the effects of RSG on T cell differentiation. After challenge with OVA, mice developed the typical pathophysiological features of asthma, including an increased number of neutrophils in the BALF and the up-regulation of IL-17. The numbers of Th17 cells and Th2 cells were also greatly elevated in the lungs. The administration of rosiglitazone reduced the pathophysiological features of asthma and decreased the up-regulated inflammatory mediators and cytokines. Furthermore, the cell viability in the co-culture system was markedly reduced by RSG. T-bet, Gata-3 and RORγt mRNA were down-regulated by RSG. These findings suggest that PPARγ is critical for airway inflammation during neutrophilic asthma, possibly due to its effect on Th cell proliferation and differentiation. These findings suggest that the therapeutic effect of rosiglitazone in neutrophilic asthma is partially due to the role of the PPARγ pathway in regulating T cell proliferation and differentiation.

DOI: 10.1016/j.imlet.2013.11.004
0501002014201520162017
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@article{Zhao2014RosiglitazoneAP, title={Rosiglitazone, a peroxisome proliferator-activated receptor-γ agonist, attenuates airway inflammation by inhibiting the proliferation of effector T cells in a murine model of neutrophilic asthma.}, author={Yan Zhao and Yi Huang and Jing He and Chang-Yi Li and Wang Deng and Xuemei Ran and Daoxin Wang}, journal={Immunology letters}, year={2014}, volume={157 1-2}, pages={9-15} }