Electrophilic PPARγ Ligands Attenuate IL-1β and Silica-Induced Inflammatory Mediator Production in Human Lung Fibroblasts via a PPARγ-Independent Mechanism

Figure 8

CDDO and PGA₁ inhibit IL-1𝛽-induced NF-𝜅B transcriptional activity in human lung fibroblasts. Primary human lung fibroblasts were transfected with a luciferase reporter, then pretreated with 20 𝜇M rosiglitazone (Rosi), 1 μM CDDO, 5 μM 15d-PGJ₂ (PGJ₂), 5 μM CAY10410 (CAY), or 15 μM PGA₁ and cotreated with of IL-1𝛽 for 24 hours as described. NF-𝜅B-dependent luciferase activity was measured in lysates as described, normalized to protein concentration, and expressed as relative light units (RLU). NF-𝜅B activation is significantly reduced in PPAR𝛾 ligand-treated fibroblasts compared to IL-1𝛽 alone (*𝑃<.01). Results are mean ± standard deviation for quadruplicate wells and are representative of 2 independent experiments that yielded similar results.