Glucocorticoid-induced apoptosis in human eosinophils: mechanisms of action.
Prominent blood and tissue eosinophilia is clinically manifested in a number of inflammatory states, particularly in allergic diseases. Corticosteroids are the most effective anti-inflammatory drugs used in the treatment of eosinophilic disorders, including bronchial asthma. Their beneficial effects result, among others, from (i) the suppression of the synthesis and the effects of eosinophil survival factors, (ii) the direct induction of eosinophil apoptosis and (iii) the stimulation of their engulfment by professional phagocytic cells. Failure of steroids to propagate apoptotic signals and to promote eosinophil clearance may explain the corticoresistance observed in a proportion of asthmatic patients. Accordingly, studies on the intracellular mechanisms involved in eosinophil corticosensitivity and resistance may provide a valuable tool for identifying new and selective molecular targets to therapeutically resolve otherwise persistent eosinophilic inflammation. In this review, the intracellular cascade of events involved in corticosteroid-mediated eosinophil apoptotic death is discussed and compared to the signalling pathway governing this process in the established model of dexamethasone-induced thymocyte apoptosis.
Druilhe
A
A
Institut National de la Santé et de la Recherche Médicale (INSERM) U408, Faculté de Médecine Xavier Bichat, Paris, France.
Létuvé
S
S
Pretolani
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D004802:Eosinophilia / Q000378:metabolism* / Q000473:pathology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019254:Genes, bcl-2; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D010586:Phagocytes / Q000502:physiology; D010770:Phosphotransferases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D005938:Glucocorticoids; D017382:Reactive Oxygen Species; D010770:Phosphotransferases