| First Author | Mastrofrancesco A | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 4 | Pages | 1001-1011 |
| PubMed ID | 24166135 | Mgi Jnum | J:207943 |
| Mgi Id | MGI:5559967 | Doi | 10.1038/jid.2013.448 |
| Citation | Mastrofrancesco A, et al. (2014) Preclinical Studies of a Specific PPARgamma Modulator in the Control of Skin Inflammation. J Invest Dermatol 134(4):1001-11 |
| abstractText | Peroxisome proliferator-activated receptor gamma (PPARgamma) antagonizes inflammatory signals by interfering with NF-kappaB nuclear translocation. Consistently, PPARgamma agonists have been proposed in various inflammatory skin disorders, but their wide use has been limited by severe side effects. Classes of compounds with specific PPARgamma agonism have been designed to selectively target inflammatory pathways. Among these compounds, GED-0507-34L has been developed and recently used in phase II clinical trials for inflammatory bowel diseases. This study was aimed at assessing the role of GED-0507-34L in preclinical models of inflammatory skin diseases. The compound modulated PPARgamma function and suppressed the inflammatory process inhibiting NF-kappaB nuclear translocation with the consequent reduction of inflammatory cytokines expression, such as IL-6, IL-8, IL-12, IL-21, IL-23, tumor necrosis factor-alpha (TNF-alpha), and cyclooxygenase-2 (COX-2) in normal human keratinocytes and lymphocytes treated with lipopolysaccharide (LPS) or TNF-alpha. Moreover, an altered proliferation and expression of differentiation markers induced by TNF-alpha were also counteracted. In psoriasis-like skin lesions elicited in mice by IL-21, topical application of GED-0507-34L reduced cellular infiltrate and epidermal hyperplasia, normalizing the differentiation process. The results indicate that GED-0507-34L possesses anti-inflammatory properties useful for the management of patients with inflammatory skin diseases including psoriasis. Phase I trial on patients is ongoing. |
