The role of PPAR-γ in macrophage differentiation and cholesterol uptake

Abstract

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), the transcription factor target of the anti-diabetic thiazolidinedione (TZD) drugs, is reported to mediate macrophage differentiation and inflammatory responses. Using PPAR-gamma-deficient stem cells, we demonstrate that PPAR-gamma is neither essential for myeloid development, nor for such mature macrophage functions as phagocytosis and inflammatory cytokine production. PPAR-gamma is required for basal expression of CD36, but not for expression of the other major scavenger receptor responsible for uptake of modified lipoproteins, SR-A. In wild-type macrophages, TZD treatment divergently regulated CD36 and class A macrophage-scavenger receptor expression and failed to induce significant cellular cholesterol accumulation, indicating that TZDs may not exacerbate macrophage foam-cell formation.

PPARα agonists inhibit nitric oxide production by enhancing iNOS degradation in LPS‐treated macrophages

“…inflammatory effects (Thieringer et al, 2000;Guyton et al, 2001;Moore et al, 2001b;Fu et al, 2002). Thus, PPARs have been shown to have in vivo relevance with inflammatory processes, and that is the reason why the mechanisms underlying these effects are highly interesting to clarify.…”

Peroxisome proliferator–activated receptor γ is expressed in airways and inhibits features of airway remodeling in a mouse asthma model☆

“…Experiments were carried out in accordance with ethical guidelines from the Comité d'Ethique en Expériementation Animale de la Region Nord-Pas de Calais. Six-to 8-week-old mice were sensitized by means of intraperitoneal injection of ovalbumin (OVA; 50 lg, Sigma) in 100 lL of alum (Imject, Pierce) or received alum only and were challenged for 20 minutes on days 14,15,16,18,19, and 20 by means of aerosol nebulization with OVA (1% in PBS) by using an ultrasonic nebulizer (System). Ciglitazone (5 3 10 ÿ5 mol/L, Alexis) in PBS or ciglitazone (5 3 10 ÿ5 mol/L) and GW9662 (5 3 10 ÿ5 mol/L, Cayman) in PBS (or vehicle) were administered by means of nebulization for 20 minutes immediately before and during each OVA challenge.…”

“…12,13 Peroxisome proliferator-activated receptors (PPARs) were also reported to regulate inflammatory responses. [14][15][16] Three subtypes of PPARs (a, b/d, and c) have been identified. 17 One of the natural ligands for PPAR-c is 15-deoxy-D-prostaglandin J2, the major metabolite from prostaglandin D2.…”

Up‐regulation of heme oxygenase‐1 expression through the Rac1/NADPH oxidase/ROS/p38 signaling cascade mediates the anti‐inflammatory effect of 15‐deoxy‐Δ12,14‐prostaglandin J2 in murine macrophages

“…However, other accumulating data suggest that the PPAR-c-independent mechanism may account for the major anti-inflammatory action of 15dPGJ 2 . For example, 15dPGJ 2 repress several pro-inflammatory genes, including inducible nitric oxide synthase (iNOS) and tumor necrosis factor-a (TNF-a) genes in macrophages derived from PPAR-cdeficient embryonic stem cells [6,7]. 15dPGJ 2 also performs its anti-inflammatory activity through direct inhibition of signaling steps leading to nuclear factor-kappa B (NF-kB) activation [8,9], eventually down-regulating expression of proinflammatory cytokines and immune mediators.…”