Significance of anti-inflammatory effects of PPARγ agonists?

TLDR: PPARγ mediated effects in the experimental setting of toll-like receptor stimulation were independent of NFκB and interferon regulatory factor, in contrast with GR action, which indicates that glucocorticoids and ligands of PPARγ could have additive therapeutic effects.

Abstract: Peroxisome proliferator activated receptor γ expression in mucosal epithelial cells seems to be crucial for its anti-inflammatory effects with respect to experimental colitis, and for maintaining homeostasis of the mucosal barrier, at least in animal models The peroxisome proliferator activated receptor γ (PPARγ) is one of three members of the PPAR family (PPARα and PPARδ), which itself is a part of the nuclear hormone receptor superfamily.1–5 Nuclear hormone receptors are transcription factors that are activated by the binding of small lipophilic ligands.6,7,8,9,10,11 They induce or repress transcription of a large number of different genes thereby influencing cellular functions. PPARγ was initially identified for its role in adipocyte differentiation and regulation of genes involved in lipid and glucose metabolism.12–15 However, activation of PPARγ also can antagonise nuclear factor κB (NFκB) action in macrophages resulting in downregulation of proinflammatory cytokines.10,16–22 Implicated in these anti-inflammatory properties, PPARγ is not only expressed in adipocytes but also in a number of other cells types, such as macrophages,9 lymphocytes, hepatocytes, and skeletal muscle. Very high expression levels are found in the colonic epithelium.23 Interestingly, the proinflammatory genes that are repressed by PPARγ overlap but are not identical to the genes that are downregulated by the glucocorticoid receptor (GR), another member of the nuclear hormone receptor superfamily which intracellularly mediates the effects of endogenous cortisol and therapeutically administrated glucocorticoids.24 PPARγ mediated effects in the experimental setting of toll-like receptor stimulation were independent of NFκB and interferon regulatory factor, in contrast with GR action.24 This indicates that glucocorticoids and ligands of PPARγ could have additive therapeutic effects. The eicosanoids 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid as well as 15deoxy-Δ12,14,-prostaglandin J2 have …