PPAR Expression in Immune Cells and the Lung

PPARs are expressed in various cells of the immune system and the lungs (Table 6.1). PPARa and PPARy are both expressed in macrophages and monocytes [51], eosinophils [52], with PPARp also being expressed in neutrophils [37]. Dendritic cells only express PPARy [53], while both PPARa and PPARy are expressed by lymphocytes [54, 55]. PPARp and PPARy are both expressed in mast cells [56], while all three isoforms are present in airway epithelial cells [57]. As for mesenchymal cells, PPARy is expressed by fibroblasts [58], while PPARa and PPARy are present in airway smooth muscle cells [59]. These distinct patterns of expression suggest that activation of different isoforms may specifically regulate the production of inflammatory mediators and cellular responses.

There is increasing evidence suggesting that PPAR receptor patterns change in various lung disease, with PPARy being the most extensively studied. Literature consensus for the role of PPARy expression in the lungs is that it is up-regulated in response to diverse inflammatory conditions providing a negative feedback loop

Table 6.1 PPARy- expressing immune and pulmonary cells

Cell type/subtype


Immune cells









Dendritic cells


Pulmonary cells





Smooth muscle


that allows natural PPARy ligands to limit inflammatory responses in the lungs [60]. There is mounting evidence that PPAR ligands affect inflammatory processes through influencing cellular immune responses. These actions overlap with corticosteroids, exerting inhibitory effects on T cells, eosinophils, neutrophils, mast cells/ basophils, and macrophages [61], with studies mostly focusing on PPARy [62].

The PPARy ligands PGJ2 and CGZ were reported to inhibit T cell proliferation [63]. PGJ2 efficiently induces T cell apoptosis and can also decrease the production of both Th1 and Th2 type cytokines from T cells [64]. Moreover, T cells treated with CGZ show decreased IFNy, IL-4, and IL-2 secretion [65]. On the other hand, PGJ2 may also potentially trigger inflammation through the induction of IL-8 expression in T cells and macrophages via MAPK and NfkB signalling [66]. In monocytes, PGJ2 and TGZ efficiently inhibit the secretion of tumour necrosis factor a (TNFa), interleukin-ip (IL- ip) and IL-6 [67 ] . PGJ2 and RGZ also decrease TNFa release and the expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase (MMP)-9 in macrophages through inhibiting the activities of AP-1, STAT, and NFkB. Moreover, both PPARa and PPARy ligands promote macrophage apoptosis as well [66, 67].

< Prev   CONTENTS   Source   Next >