The concept of the inflammasome and its rheumatologic implications |
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| Affiliation: | 1. Department of Rheumatology, CHRU de Besançon, boulevard Fleming, 25030 Besançon, France;2. University of Franche-Comté, UPRES EA 4266 Pathogens & Inflammation Laboratory, SFR FED4234, Besançon, France;3. Department of Virology, CHRU de Besançon, place Saint-Jacques, 25030 Besançon, France;1. Department of Radiology, Medical Faculty, Ataturk University, 25240 Erzurum, Turkey;2. Department of Cardiovascular Surgery, Medical Faculty, Ataturk University, Erzurum, Turkey;1. Service de rhumatologie, CHRU de Besançon, boulevard Fleming, 25030 Besançon, France;2. EA 4266 (agents pathogènes et inflammation), université de Franche-Comté, 25030 Besançon, France;3. Service de médecine nucléaire, CHRU de Besançon, boulevard Fleming, 25030 Besançon, France;4. EA 4267, université de Franche-Comté, Besançon, France;1. Department of Rheumatology, CHU d’Amiens, University of Picardie Jules Verne, 80054 Amiens, France;2. Department of Rheumatology, CHU de Rouen, University of Rouen, 76031 Rouen, France;3. Unité Inserm U1088, Université de Picardie-Jules-Verne, 80054 Amiens, France;1. Université de Lyon, Department of Dermatology, Hôpital Édouard-Herriot, 69003 Lyon, France;2. Inserm UMR1033, Université de Lyon, Department of Rheumatology, Hôpital Édouard-Herriot, Hospices Civils de Lyon, 69003 Lyon, France;1. Department of Neurology, Medical University of Lublin, Poland;2. Department of Biochemistry, Medical University of Lublin, Poland;3. 2nd Department of Radiology, Medical University of Lublin, Poland |
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| Abstract: | The inflammasome is a proteolytic complex that regulates IL1β and IL-18 secretion in macrophages and dendritic cells. Its plays a vital role in the control of the inflammatory and cellular responses to infectious and danger signals and is an essential part of the innate immune system. Four different inflammasomes have been identified so far, and the NLRP3-inflammasome has been the best-studied in relation to human disease. Activation of the NLRP3-inflammasome by microcrystals, such as monosodium urate (MSU) and basic calcium phosphate (BCP) crystals, leads to IL1β release, which in turn triggers local inflammation. Dysfunction of the NLRP3-inflammasome due to mutations of the NLRP3 gene is the cause of the auto-inflammatory syndrome CAPS. The symptoms and signs of inflammation in both conditions respond to IL1 blockade. IL1 inhibitors have also been used successfully in other idiopathic inflammatory diseases, suggesting that dysregulated inflammasome activity contributes to the pathogenesis of multiple diseases, but the precise underlying mechanisms remain to be identified. |
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| Keywords: | IL1β Inflammasome Auto-inflammatory disorders Gout |
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