Yongchun Shen, Lei Chen, Tao Wang, Fuqiang Wen

“ Considerations for Targeting PPARγ in the Treatment of AMH Although several studies have suggested that PPARγ is involved in AMH and that PPARγ agonists inhibit AMH, there is still a long road ahead before laboratory studies can be translated to the clinic. For one thing, the pathogenesis of chronic airway inflammatory diseases such as COPD, asthma, and CF is extremely complicated. Only a few studies, most of them descriptive, have directly investigated the role of PPARγ and PPARγ ligand in AMH. As a result, the signaling pathways affected by PPARγ or PPARγ agonists remain poorly understood. ”

“ The authors concluded that PPARγ exerts an anti-inflammatory effect by stimulating MUC1/Muc1 expression, which then blocks the production of TNF-α/IL-8 induced by phorbol 12-myristate 13-acetate in airway epithelial cells [44] . In addition, PPARγ plays an essential role in the pathway through which monocyte/ macrophage-derived microparticles activate NF-κB and ultimately induce upregulation of proinflammatory mediators in human lung epithelial cells [45] . ”

“ For instance, cigarette smoke, neutrophil elastase, and P. aeruginosa proteases are well-known inflammatory stimuli that can cause significant inflammatory responses, which result in goblet cell metaplasia and hyperplasia, leading in turn to mucin overproduction and mucus hypersecretion in airways [22] [23] [24] . Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) , interleukin (IL) -1β, IL-6, IL-8, IL-13, and IL-17 can upregulate the expression of MUC5AC, the marker of goblet cell metaplasia, through different signaling pathways [25] [26] [27] [28] [29] . ”