| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Mastrofrancesco, Arianna Kovacs, Daniela Sarra, Massimiliano Bastonini, Emanuela Cardinali, Giorgia Aspite, Nicaela Camera, Emanuela Chavatte, Philippe Desreumaux, Pierre Monteleone, Giovanni Picardo, Mauro |
| Description |
Country affiliation: Italy Author Affiliation: Mastrofrancesco A ( Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy.); Kovacs D ( Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy.); Sarra M ( Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.); Bastonini E ( Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy.); Cardinali G ( Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy.); Aspite N ( Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy.); Camera E ( Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy.); Chavatte P ( Laboratoire de Chimie Thérapeutique, Faculté des Sciences Pharmaceutiques et Biologiques, Université Lille-Nord de France, Lille, France.); Desreumaux P ( University Lille Nord de France, Inserm U995, Huriez Hospital, Hepato-Gastroenterology Department, Lille, France.); Monteleone G ( Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.); Picardo M ( Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, Rome, Italy.) |
| Abstract |
Peroxisome proliferator-activated receptor γ (PPARγ) antagonizes inflammatory signals by interfering with NF-κB nuclear translocation. Consistently, PPARγ 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 PPARγ 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 PPARγ function and suppressed the inflammatory process inhibiting NF-κB 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- (TNF- ), and cyclooxygenase-2 (COX-2) in normal human keratinocytes and lymphocytes treated with lipopolysaccharide (LPS) or TNF- . Moreover, an altered proliferation and expression of differentiation markers induced by TNF- 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. |
| File Format |
HTM / HTML |
| ISSN |
0022202X |
| e-ISSN |
15231747 |
| Journal |
Journal of Investigative Dermatology |
| Issue Number |
4 |
| Volume Number |
134 |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2014-04-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Discipline Dermatology Active Transport, Cell Nucleus Drug Effects Aniline Compounds Therapeutic Use Inflammation Drug Therapy Metabolism Phenylpropionates Propionates Skin Pathology Chemistry Animals Biopsy Cell Adhesion Cell Proliferation Cells, Cultured Cyclooxygenase 2 Cytokines Epidermis Keratinocytes Cytology Lipopolysaccharides Mice Mice, Inbred C57bl Nf-kappa B Protein Binding Psoriasis Rna Interference Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology Dermatology |
