Involvement of the peripheral benzodiazepine receptor in the development of cutaneous pathology in Mrl/Lpr mice.
Mrl/Lpr mice develop inflammatory pathologies similar to human lupus erythematosus (LE). In that model, we showed a protective effect of different peripheral benzodiazepine receptor (PBR) ligands: PK 11195, Ro5-4864 and the newly described SSR180575 on the development of the cutaneous lesions. Specifically, we evidenced that a chronic treatment at 3 mg/kg per i.p. for 30 days prevented acanthosis, hyperkeratosis and generation of dermal infiltrates as compared with control untreated mice. In addition, using a specific polyclonal anti mouse PBR antibody, we characterized PBR expression in the skin lesions, and we observed that PBR expression in the epidermal component was increased when Mrl/Lpr mice developed the pathology and diminished upon PBR ligand treatment. PBR expression modulation together with the protective effects of its ligands further reinforce the role that PBR may play in the regulation of inflammation processes. Provided the exact mechanism of action that accounts for PBR action in that process is elucidated, these data support new therapeutic applications for specific potent PBR ligands.
Bribes
Estelle
E
Immunology-Oncology Department, Sanofi-Synthelabo Recherche, 371 avenue du Prof. Joseph Blayac, 34184 Cedex 04, Montpellier, France. estelle.bribes@sanofi-synthelabo.com
Galiegue
Sylvaine
S
Bourrie
Bernard
B
Casellas
Pierre
P
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D004195:Disease Models, Animal; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines; D008024:Ligands; D008178:Lupus Erythematosus, Cutaneous / Q000276:immunology / Q000473:pathology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011963:Receptors, GABA-A / Q000502:physiology*; D012867:Skin / Q000473:pathology*
D019138:Antibodies, Blocking; D058785:GABA-A Receptor Agonists; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; C037850:PK 11195