The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis
| Autor: | Pedro Zapater, Victoria Bachiller, Noé Quesada-Vázquez, Enrique de-Madaria, Claudia Martínez-Cardona, Francisco Algaba-Chueca, Beatriz Lozano-Ruiz, José M. González-Navajas, Fabián Tarín, Rubén Francés, José Such |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Inflammasomes Endocrinology Diabetes and Metabolism Interleukin-1beta Inflammation Systemic inflammation Monocytes Pathogenesis 03 medical and health sciences AIM2 0302 clinical medicine medicine Humans Prospective Studies RNA Messenger Aged Immunity Cellular Hepatology business.industry Interleukin-18 Gastroenterology Inflammasome Middle Aged medicine.disease DNA-Binding Proteins 030104 developmental biology Pancreatitis Acute Disease Immunology Acute pancreatitis Female 030211 gastroenterology & hepatology medicine.symptom business Inflammasome complex medicine.drug |
| Zdroj: | Pancreatology. 17:364-371 |
| ISSN: | 1424-3903 |
| DOI: | 10.1016/j.pan.2017.03.006 |
| Popis: | Background Acute pancreatitis is an inflammatory disorder of the pancreas that is responsible for significant morbidity and mortality. The inflammasome pathway has acquired significant relevance in the pathogenesis of many inflammatory disorders, but its role in patients with acute pancreatitis still awaits clarification. Methods We performed a prospective study in which 27 patients with acute pancreatitis and 16 healthy controls were included. We isolated peripheral blood mononuclear cells (PBMCs) and we assessed the expression and activation of different inflammasomes as well as their association with the clinical course of the disease. Results Our results show that PBMCs from patients with acute pancreatitis have elevated expression of several components of the inflammasome complex, including the inflammasome-forming receptor absent in melanoma 2 (AIM2), early during the onset of the disease. Activation of the AIM2 or NLRP3 inflammasomes in PBMCs from patients with acute pancreatitis results in exacerbated IL-1β and IL-18 production compared with PBMCs from healthy controls. Furthermore, both AIM2 mRNA expression and AIM2-mediated production of IL-1β by PBMCs correlated with increased systemic inflammation in these patients. Last, AIM2 expression was further increased in those patients that developed transient or persistent organ failure (moderate or severe acute pancreatitis). Conclusions Our data demonstrates that AIM2 inflammasome expression and activation is increased early during the course of acute pancreatitis, and suggests that AIM2 activation may affect systemic inflammation and organ failure in these patients. |
| Databáze: | OpenAIRE |
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