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EnglishObjective. IL-1β plays a key role in the pathogenesis of Schnitzler's syndrome (SS). We have investigated inflammasome activity in peripheral blood mononuclear cells (PBMCs) from a patient affected by a variant type of SS. Methods. PBMCs were purified by Ficoll and examined for ability to secrete IL-1β and -18, expression and function of the P2X7 receptor and expression of apoptosis-associated speck-like protein containing a caspase recruitment domaine (ASC) and NOD-like receptor protein 3 (NLRP3) before and after the therapy with steroid. Furthermore, extracellular adenosine 5'-triphosphate (ATP) blood levels were determined by luciferase assay. Expression of inflammasome components was measured by real time PCR and western blotting. Results. PBMCs of patient with SS showed a high, spontaneous and lipopolysaccharide-stimulated, IL-1β release but low response to stimulation with the P2X7 agonist benzoyl ATP. P2X7 expression was several fold increased, whereas ASC expression was dramatically decreased compared with PBMCs from healthy controls. NLRP3 expression was unchanged. Prednisone treatment induced remission of clinical symptoms and normalized IL-1β secretion and P2X7 and ASC expression. Conclusion. These findings reveal the presence of an overall derangement of the inflammasome and IL-1β processing and release in SS.
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| Titolo: | Dysfunctional inflammasome in Schnitzler's syndrome |
| Autori: | |
| Data di pubblicazione: | 2009 |
| Rivista: | |
| Abstract: | Objective. IL-1β plays a key role in the pathogenesis of Schnitzler's syndrome (SS). We have investigated inflammasome activity in peripheral blood mononuclear cells (PBMCs) from a patient affected by a variant type of SS. Methods. PBMCs were purified by Ficoll and examined for ability to secrete IL-1β and -18, expression and function of the P2X7 receptor and expression of apoptosis-associated speck-like protein containing a caspase recruitment domaine (ASC) and NOD-like receptor protein 3 (NLRP3) before and after the therapy with steroid. Furthermore, extracellular adenosine 5'-triphosphate (ATP) blood levels were determined by luciferase assay. Expression of inflammasome components was measured by real time PCR and western blotting. Results. PBMCs of patient with SS showed a high, spontaneous and lipopolysaccharide-stimulated, IL-1β release but low response to stimulation with the P2X7 agonist benzoyl ATP. P2X7 expression was several fold increased, whereas ASC expression was dramatically decreased compared with PBMCs from healthy controls. NLRP3 expression was unchanged. Prednisone treatment induced remission of clinical symptoms and normalized IL-1β secretion and P2X7 and ASC expression. Conclusion. These findings reveal the presence of an overall derangement of the inflammasome and IL-1β processing and release in SS. |
| Handle: | http://hdl.handle.net/11392/1378259 |
| Appare nelle tipologie: | 03.1 Articolo su rivista |
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