Ligands of the peripheral benzodiazepine receptor have therapeutic effects in pneumopathies in vivo.
In this study, we documented the effects of different peripheral benzodiazepine receptor (PBR) ligands: PK 11195, Ro5-4864 and the newly described SSR 180575 on the development of pulmonary inflammation in vivo. To this aim, we used MRL/lpr mice that develop pathological signs similar to the human lupus erythematosus (LE) signs. We found that a chronic treatment (at 3 mg/kg per i.p. for 30 days) with PBR ligands had a significant beneficial therapeutic action and decreased the inflammatory pulmonary responses and alveolitis onset. When analyzing PBR expression in inflamed tissues, we observed that in addition to the infiltrated leukocytes, PBR was expressed in the bronchial epithelium, and especially we evidenced for the first time that PBR in expressed in Clara cells. Interestingly, we observed that PBR expression in those cells was reduced when MRL/lpr mice developed the pathology and restored upon PBR ligand treatment. These original findings support a role of PBR in pulmonary inflammatory process and suggest new therapeutic applications in auto immune disorders for specific potent PBR ligands.
Bribes
Estelle
E
Immunology-Oncology Department, Sanofi-Synthelabo Recherche, 371, rue du Prof. Joseph Blayac, 34184 Montpellier Cedex 04, France. estelle.bribes@sanofi-synthelabo.com
Bourrie
Bernard
B
Casellas
Pierre
P
D000081:Acetamides / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D001570:Benzodiazepinones / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D058787:GABA-A Receptor Antagonists; D007211:Indoles / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D008024:Ligands; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D015394:Molecular Structure; D011014:Pneumonia / Q000188:drug therapy* / Q000473:pathology; D011963:Receptors, GABA-A / Q000032:analysis / Q000378:metabolism*
D000081:Acetamides; D001570:Benzodiazepinones; D058787:GABA-A Receptor Antagonists; D007211:Indoles; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; C456740:SSR180575; C028513:4'-chlorodiazepam; C037850:PK 11195