PPARγ in emphysema: blunts the damage and triggers repair?
Neil J. Kelly, Steven D. Shapiro
Neil J. Kelly, Steven D. Shapiro
Published February 24, 2014
Citation Information: J Clin Invest. 2014;124(3):978-980. https://doi.org/10.1172/JCI74417.
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Commentary

PPARγ in emphysema: blunts the damage and triggers repair?

Abstract

Cigarette smoke is the most common cause of pulmonary emphysema, which results in an irreversible loss of lung structure and function. Th1 and Th17 immune responses have been implicated in emphysema pathogenesis; however, the drivers of emphysema-associated immune dysfunction are not fully understood. In this issue of the JCI, Shan and colleagues found that peroxisome proliferator–activated receptor γ (PPARγ) is downregulated in APCs isolated from the lungs of emphysematous chronic smokers and mice exposed to cigarette smoke. Furthermore, treatment with a PPARγ agonist prevented emphysema development and appeared to reduce emphysema-associated lung volume expansion in mice exposed to cigarette smoke. Further work will need to be done to evaluate the potential of PPARγ agonists to restore lung capacity in emphysematous patients.

Authors

Neil J. Kelly, Steven D. Shapiro

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Figure 1

Proposed role of PPARγ in pulmonary emphysema pathogenesis.

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Proposed role of PPARγ in pulmonary emphysema pathogenesis. Smoking lead...
Smoking leads to the acquisition of a pathogenic phenotype in lung mDCs, characterized by ciglitazone-reversible downregulation of PPARγ and upregulation of SPP1. Pathogenic mDCs then direct the differentiation of Th1 and Th17 helper T lymphocytes, whose cytokines IFN-γ and IL-17A, respectively, trigger the release of the macrophage elastase MMP12 and accompanying alveolar destruction.