Preclinical Studies of a Specific PPARγ Modulator in the Control of Skin Inflammation

摘要: Peroxisome proliferator–activated receptor γ (PPARγ) antagonizes inflammatory signals by interfering with NF-κB nuclear translocation. Consistently, PPARγ agonists have been proposed in various skin disorders, but their wide use has limited severe side effects. Classes of compounds specific agonism designed to selectively target pathways. Among these compounds, GED-0507-34L developed and recently used phase II clinical trials for bowel diseases. This study was aimed at assessing the role preclinical models The compound modulated function suppressed process inhibiting translocation consequent reduction cytokines expression, such as IL-6, IL-8, IL-12, IL-21, IL-23, tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) normal human keratinocytes lymphocytes treated lipopolysaccharide (LPS) or TNF-α. Moreover, an altered proliferation expression differentiation markers induced TNF-α were also counteracted. In psoriasis-like lesions elicited mice topical application reduced cellular infiltrate epidermal hyperplasia, normalizing process. results indicate that possesses anti-inflammatory properties useful management patients diseases including psoriasis. Phase I trial on is ongoing.